AJP-Heart and Circulatory Physiology Podcasts: Recent Episodes
American Physiological Society
The literature shows that the incidence of heart failure with preserved ejection fraction (HFpEF) increases significantly in postmenopausal women, but how can researchers study the underlying mechanisms? In our latest episode, Dr. Jonathan Kirk (Loyola University Chicago) interviews lead author Dr. Mei Methawasin (University of Missouri, Columbia) and expert Dr. Glen Pyle (University of Guelph) about the recent study by Methawasin and co-authors investigating sex differences, menopause and HFpEF. The authors created an animal model that resembles HFpEF in women undergoing natural menopause by using 4-vinylcyclohexene dioxide (VCD) to induce “ovary-intact” menopause, combined with the 2hit regimen (HFpEF inducing regimen) to model postmenopausal HFpEF. Combining echocardiography, pressure-volume and single-cell analyses, the authors found that VCD mice, compared to ovariectomized mice and premenopausal mice, have higher testosterone levels compared to other models. By developing this robust phenotype animal model, the authors open new avenues for investigating therapeutic targets in other hormones beyond estrogen alone. Ready to explore the estrobolome, the importance of animal models of human disease, and the complex family of hormones comprising estrogen? Listen now.
Mei Methawasin, Joshua Strom, Vito A. Marino, Jochen Gohlke, Julia Muldoon, Shelby R. Herrick, Robbert van der Piji, John P. Konhilas, Henk Granzier An ovary-intact postmenopausal HFpEF mouse model; menopause is more than just estrogen deficiency Am J Physiol Heart Circ Physiol, published March 10, 2025. DOI: 10.1152/ajpheart.00575.2024
What is the role of ferroptosis, programmed cell death characterized by intracellular iron accumulation and lipid peroxidation, in the context of ischemic injury related to heart transplantation? In this episode, Associate Editor Dr. Amanda LeBlanc (University of Louisville) interviews authors Dr. Kenneth Liao and Dr. Nandan Mondal (both at Baylor College of Medicine), along with expert Dr. Zachary Kiernan (Virginia Commonwealth University) about the latest study by Li et al. The authors found that prolonged cold storage increases the susceptibility of hearts donated after brain death (DBD) to ferroptotic cell death. In contrast, however, the authors found that warm ischemic injury increased the risk for ferroptotic cell death in hearts donated after circulatory death (DCD). Li et al. found that targeting ferroptosis could be beneficial for optimizing cold preservation for DBD hearts, while interventions for DCD hearts should focus on the early phase of warm ischemia. Heart transplantation is the gold standard therapy for patients with medically refractory advanced heart failure. However, demand greatly exceeds supply of donor hearts. Listen as we discuss the current state of the heart transplantation field and the many challenges it faces.
Shiyi Li, Katherine V. Nordick, Abdussalam E. Elsenousi, Rishav Bhattacharya, Randall P. Kirby, Adel M. Hassan, Camila Hochman-Mendez, Todd K. Rosengart, Kenneth K. Liao, and Nandan K. Mondal Warm-ischemia and Cold Storage Induced Modulation of Ferroptosis Observed in Human Hearts Donated After Circulatory Death and Brain Death Am J Physiol Heart Circ Physiol, published March 28, 2025. DOI: 10.1152/ajpheart.00806.2024
Can hormonal fluctuations across a single menstrual cycle alter arterial wave reflections and wasted pressure effort? In this episode, Associate Editor Dr. Jonathan Kirk (Loyola University Chicago) interviews author Dr. Ninette Shenouda (University of Delaware) and expert Dr. Sarah Baker (Mayo Clinic) about the latest study by Shenouda et al. investigating sex differences and ventricular arterial interactions. The authors wanted to understand how strategic phases of the menstrual cycle might affect the relationship between the left ventricle (LV) and the arterial system, as this relationship is crucial for maintaining adequate cardiac output and blood pressure. Given the established beneficial effects of estradiol on the vasculature, the authors hypothesized that their cohort of naturally menstruating premenopausal women would have favorable reductions in total peripheral resistance and favorable changes in the arterial wave reflection profile during the high hormone cycle phases, compared to age matched men. What were the unexpected findings? Listen now to find out.
Ninette Shenouda, Joseph M. Stock, Nicholas V. Chouramanis, Zoe R. Lincoln, Megan M. Wenner, Julio A. Chirinos, and David G. Edwards Favorable alterations in ventricular-arterial interactions across the menstrual cycle in healthy premenopausal women Am J Physiol Heart Circ Physiol, published February 28, 2025. DOI: 10.1152/ajpheart.00363.2024
In this episode, Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) interviews authors Dr. Oliver H. Wearing (University of British Columbia), Dr. Naomi C. Chesler (University of California Irvine), Dr. Mitchel J. Colebank (University of South Carolina), Dr. Timothy A. Hacker (University of Wisconsin-Madison), Dr. John N. Lorenz (University of Cincinnati), and Dr. Christopher R. West (University of British Columbia) about their new Guidelines in Cardiovascular Research article. This must-read Guidelines article provides a thorough overview of ventricular pressure-volume (PV) measurements in the mouse heart. PV measurements are an invasive method for assessment of heart function, and if done correctly, can provide researchers with valuable information about heart hemodynamics and the relationship between changes in ventricular pressure and volume during a cardiac cycle. The authors discuss PV measurements as the gold standard for assessing cardiac in vivo function. How do PV measurements differ from, and provide a complement to, echocardiography measurements? Listen and find out more.
Oliver H. Wearing, Naomi C. Chesler, Mitchel J. Colebank, Timothy A. Hacker, John N. Lorenz, Jeremy A. Simpson, and Christopher R. West Guidelines for assessing ventricular pressure-volume relationships in rodents Am J Physiol Heart Circ Physiol, published January 2, 2025. DOI: 10.1152/ajpheart.00434.2024
In our latest episode, Dr. Jeff Saucerman (University of Virginia) interviews authors Dr. Naomi Chesler (University of California, Irvine) and Dr. Mitchel Colebank (University of South Carolina) about their new Guidelines in Cardiovascular Research article on incorporating mechanistic modeling into the analysis of experimental and clinical data to identify possible mechanisms of (ab)normal cardiovascular physiology. The authors’ goal is to provide a consensus document that identifies best practices for in silico computational modeling in cardiovascular research. These guidelines provide the necessary methods for mechanistic model development, model analysis, and formal model calibration using fundamentals from statistics. Colebank et al. outline rigorous practices for computational, mechanistic modeling in cardiovascular research and discuss its synergistic value to experimental and clinical data. Would you like to understand how to apply a cone of uncertainty to your experimental data? Listen now to find out more.
Mitchel J. Colebank, Pim A. Oomen, Colleen M. Witzenburg, Anna Grosberg, Daniel A. Beard, Dirk Husmeier, Mette S. Olufsen, and Naomi C. Chesler Guidelines for mechanistic modeling and analysis in cardiovascular research Am J Physiol Heart Circ Physiol, published August 6, 2024. DOI: 10.1152/ajpheart.00253.2024
In this episode of Behind the Bench, we are talking with Hannah Cizauskas about her first, first-author article published in AJP-Heart and Circ. Born and raised in Detroit, Hannah moved to Chicago for what she thought would be just one rotation outside of the cancer genetics field. This led Hannah to work on a project related to atrial fibrillation and contractile dysfunction in Dave Barefield’s lab at Loyola University Chicago’s Cellular and Molecular Physiology Department. Now in the fourth year of her PhD, Hannah is a dog mom to Jake, she loves reading STEMinist novels, and she is researching sarcomere dysfunction in the context of AFib. Listen to this engaging interview with co-hosts Dr. Tommy Martin and Dr. Charlotte Usselman to find out more.
Hannah E. Cizauskas, Hope V. Burnham, Azaria Panni, Alexandra Peña, Alejandro Alvarez-Arce, M. Therese Davis, Kelly N. Araujo, Christine E. Delligatti, Eby Edassery, Jonathan A. Kirk, Rishi Arora, and David Y. Barefield Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation Am J Physiol Heart Circ Physiol, published August 5, 2024. DOI: 10.1152/ajpheart.00148.2024
In our latest episode, Executive Editor Kara Hansell Keehan interviews lead author Dr. Michaela Patterson and first author Kaelin Akins (both at the Medical College of Wisconsin) along with expert Dr. Ana Vujic (University of Cambridge) about the new study by Akins et al. Given that the heart has limited regenerative potential, repairing damage to cardiomyocytes after a heart attack is particularly challenging. Cardioregeneration researchers worldwide are searching for potential targets that can stimulate cardiomyocyte proliferation and cardiac regeneration. However, because cardiomyocytes can undergo incomplete cell division, multinucleation, and polyploidization, it is difficult to study true cardiomyocyte proliferation. Akins et al. examined the effect of Runx1 on cardiomyocyte cell cycle during postnatal development and cardiac regeneration using cardiomyocyte-specific gain- and loss-of-function mouse models. Listen now to learn more about how the authors determined that Runx1 is sufficient but not required for cardiomyocyte cell cycle activation.
Kaelin A. Akins, Michael A. Flinn, Samantha K. Swift, Smrithi V. Chanjeevaram, Alexandra L. Purdy, Tyler Buddell, Mary E. Kolell, Kaitlyn G. Andresen, Samantha Paddock, Sydney L. Buday, Matthew B. Veldman, Caitlin C. O’Meara, Michaela Patterson Runx1 is sufficient but not required for cardiomyocyte cell-cycle activation Am J Physiol Heart Circ Physiol, published July 21, 2024. DOI: 10.1152/ajpheart.00782.2023
What is the impact of central insulin on muscle sympathetic nerve activity (MSNA) and vascular conductance in the absence of peripheral insulin delivery? Listen as Associate Editor Dr. Jason Carter (Baylor University) interviews authors Neil McMillan and Dr. Jackie Limberg (both at University of Missouri), along with expert Dr. Manda Keller-Ross (University of Minnesota), about the new Short Report by McMillan et al. To gain a better understanding of the central sympathoexcitatory effects of insulin in humans, the authors recruited two groups of young, healthy individuals. One group served as a time control and the other group received intranasal insulin administration. McMillan et al. measured MSNA from the fibular nerve, combined with continuous monitoring of blood pressure and leg blood flow, before and after insulin administration. Limberg, McMillan and co-authors found that only the individuals who received insulin exhibited an increase in efferent sympathetic nervous system activity, which was coupled with peripheral vasoconstriction and increases in arterial blood pressure. How does this research influence our mechanistic understanding of the sympathetic and hemodynamic response to insulin? Listen now to find out.
Neil J. McMillan, Dain W. Jacob, Brian Shariffi, Jennifer L. Harper, Glen E. Foster, Camila Manrique-Acevedo, Jaume Padilla, and Jacqueline K. Limberg Effect of acute intranasal insulin administration on muscle sympathetic nerve activity in healthy young adults Am J Physiol Heart Circ Physiol, published July 3, 2024. DOI: 10.1152/ajpheart.00253.2024
Sometimes experimental results are serendipitous. Listen as Associate Editor Dr. Crystal Ripplinger (University of California, Davis) talks with authors Dr. Nikki Posnack and Devon Guerrelli (both at Children’s National Hospital and The George Washington University School of Engineering and Applied Science), along with expert Dr. Silvia Marchiano (University of Washington), about the new research by Guerrelli et al. published in our Call for Papers on Excitation-Contraction Coupling, Electrophysiology, and Arrhythmias. The Posnack Lab typically investigates environmental chemicals and their impact on cardiac function using microelectrode arrays to record electrical signals from human iPS cells. When performing cardiotoxicity experiments, the authors realized that their baseline measurements varied significantly between their different studies, making it difficult to combine datasets. In doing the legwork to identify potential sources of variability and improve their own internal lab protocols, the authors focused on the reproducibility of their experimental measurements using human iPSCs. Listen as we discuss important recommendations for investigators using these cells to improve their experimental reproducibility.
Devon Guerrelli, Jenna Pressman, Shatha Salameh, and Nikki Posnack hiPSC-CM Electrophysiology: Impact of Temporal Changes and Study Parameters on Experimental Reproducibility Am J Physiol Heart Circ Physiol, published June 9, 2024. DOI: 10.1152/ajpheart.00631.2023
Hormone modulation therapy is a growing area of research in cardiovascular science related to a number of factors, such as menopause and andropause, cancers in hormone-producing organs, as well as gender-affirming hormone therapy. So how do scientists and clinicians measure, monitor, and balance applications of hormone therapy? In our latest podcast, Associate Dr. Keith Brunt interviews authors Dr. Chantal Rytz (University of Calgary) and Dr. Sofia Ahmed (University of Alberta), along with expert Dr. Nina Stachenfeld (John B. Pierce Laboratory/Yale School of Medicine) about the recent article by Rytz et al. The authors review the use of estrogen in adult transgender, non-binary and gender diverse individuals who are medically managed with hormone modulation therapy for gender affirmation. Their findings indicate that the rate at which serum estrogen concentrations change may be important in order to optimize cardiovascular health and manage risk factors for obesity, hyperlipidemia, and elevated blood pressure. How should scientists account for and explore the hormone state of individuals within a cardiovascular context to improve the foundation of evidence for hormone modulation therapies for clinicians? Listen and learn more.
Chantal L. Rytz, Keila Turino Miranda, Paul E. Ronksley, Nathalie Saad, Satish R. Raj, Ranjani Somayaji, Sandra M. Dumanski, Heather Ganshorn, Dina N. Greene, David Collister, Amelia M. Newbert, Lindsay Peace, Sofia B. Ahmed Association between Serum Estradiol and Cardiovascular Health among Transgender Adults Using Gender-Affirming Estrogen Therapy Am J Physiol Heart Circ Physiol, published July 15, 2024. DOI: 10.1152/ajpheart.00151.2024
While decreased IL-33 signaling has been associated with preeclampsia, the mechanisms linking this signaling pathway to disease pathophysiology are not well understood. In this episode, Associate Editor Dr. Amanda LeBlanc (University of Louisville) interviews author Dr. Denise Cornelius (University of Mississippi Medical Center) and expert Dr. Stella Goulopoulou (Loma Linda University) about the new research study by Wang et al. Using the Reduced Uterine Perfusion Pressure (RUPP) rat model, the authors found evidence that mechanistically links reduced IL-33 with the inflammatory response and vascular dysfunction present in preeclampsia. Is the IL-33 signaling pathway a possible clinical therapeutic target for the treatment of preeclampsia? Listen now to learn more.
Xi Wang, Corbin Shields, Geilda Tardo, Greg Peacock, Emily Hester, Marissa Anderson, Jan M. Williams, Denise C. Cornelius IL-33 supplementation improves uterine artery resistance and maternal hypertension in response to placental ischemia Am J Physiol Heart Circ Physiol, published April 3, 2024. DOI: 10.1152/ajpheart.00045.2024
In this episode, Associate Editor Dr. Jonathan Kirk (Loyola University Chicago) interviews author Dr. Ed Lesnefsky (Richmond Department of Veterans Affairs Medical Center and Virginia Commonwealth University) and expert Dr. Chi Fung Lee (Oklahoma Medical Research Foundation) about the new Methods and Resources article by Chen et al. published in our Call for Papers on Impact of Aging on the Cardiovascular System. Lesnefsky and coauthors advanced a technique of isolating mitochondria with an emphasis on integrity of the mitochondrial organelles, their function, purity and characterization in order to develop benchmarks in the field for quality control to support collaboration across laboratories. In their research, the authors focus on mitochondrial-driven age-enhanced disease and on mitochondrial defects due to aging, which potentially increase the susceptibility of elderly patients’ hearts to cardiovascular disease. Well-known techniques exist for isolating specific mitochondria populations in mouse hearts. However, Lesnefsky and collaborators found that this resulted in not enough sample to properly interrogate. Therefore Lesnefsky and coauthors investigated whether they could isolate one combined mixed population of mitochondria with a “wild type” physiological model of aging, and whether or not that would that reflect the phenotype. Listen as we discuss the importance of studying mitochondria in an aging model as well as the strategy Lesnefsky and colleagues used to develop their protocol for isolating a mixed mitochondria population. Don’t miss the last few minutes of this conversation for pro tips about the value of networking and career-long mentors. Listen now.
Qun Chen, Jeremy Thompson, Ying Hu, and Edward J. Lesnefsky Aging-induced mitochondrial dysfunction: two distinct populations of mitochondria versus a combined population Am J Physiol Heart Circ Physiol, published January 12, 2024. DOI: 10.1152/ajpheart.00363.2023
In our latest episode, Consulting Editor Dr. Kristine DeLeon-Pennell (Medical University of South Carolina) interviews fellow co-authors Dr. Charlotte Usselman (McGill University), Dr. Judy Regensteiner (University of Colorado Anschutz Medical Campus), Dr. Kerrie Moreau (University of Colorado Anschutz Medical Campus), Dr. Austin Robinson (Indiana University Bloomington), Dr. Jesse Moreira-Bouchard (Boston University), and Dr. Quin Denfeld (Oregon Health and Science University) about their recently published guidelines on the use of sex and gender in cardiovascular research. Until recently, the effects of sex and gender in cardiovascular research have been largely ignored in research design and reporting. The result is that women and gender diverse individuals have been understudied in basic and clinical research, leading to a lack of understanding of sex and gender in cardiovascular health and disease. The goal of these guidelines is to provide researchers with practical and actionable advice on best practices to include sex and gender considerations in study design, data collection, analysis, and interpretation. As Dr. Judy Regensteiner points out, “We have to make it doable. We can’t just say, ‘Go do this.’ We have to show people how to do it.” Ready to get started? Listen now to learn more.
Charlotte W. Usselman, Merry L. Lindsey, Austin T. Robinson, Beth A. Habecker, Chloe E. Taylor, W. David Merryman, Derek Kimmerly, Jeffrey R. Bender, Judith G. Regensteiner, Kerrie L. Moreau, Louise Pilote, Megan M. Wenner, Myles O’Brien, Timur O. Yarovinsky, Nina S. Stachenfeld, Nisha Charkoudian, Quin E. Denfeld, Jesse D. Moreira-Bouchard, W. Glen Pyle, and Kristine Y. DeLeon-Pennell Guidelines on the use of sex and gender in cardiovascular research Am J Physiol Heart Circ Physiol, published December 21, 2023. DOI: 10.1152/ajpheart.00535.2023
After a yearlong hiatus, Behind the Bench is back, listeners! In this episode, we welcome back our B2B co-hosts Dr. Charlotte Usselman and Dr. Tommy Martin, who get the story behind the story from the one and only Dr. DeWayne Townsend, corresponding author of the recently published study by Stevens et al. Trust me, you are going to love listening to DeWayne talk about science! As DeWayne rightly points out, if we want to understand a disease before it's a disease, we have to model it in order to figure it out. From the “dastardly Krebs cycle” to grinding up hearts and shouting “fire in the hole!” before using the mouse heart pulverizer (it’s a thing), Dewayne brings to this conversation his best science sound effects, wise insights, and a friendly PSA to contact your Congressional representatives and advocate for science funding. We discuss the resiliency of physiology and the redundancies in the heart that enable scientists to knockout things thought to be important, and as DeWayne points out, the body can still handle it. We cover DeWayne’s interesting path from vet school to cardiovascular physiology, and his best advice to trainees. How do you deal with being wrong most of the time? According to DeWayne, when another beautiful hypothesis is slain by data, push on! It is a slog. Keep going and try to find a way to move the needle. While you’re at it, DeWayne suggests that you learn how to fix your own equipment, try not to drink too much caffeine, and be inspired by other scientists, especially when that scientist is your Dad.
Jackie A. Stevens, Tyler C. Dobratz, Kaleb D. Fischer, Alexandria Palmer, Kira Bourdage, Anne J. Wong, Hector Chapoy-Villanueva, Daniel J. Garry, Julia C. Liu, Matthew W. Kay, Sarah Kuzmiak-Glancy, and DeWayne Townsend Mechanisms of reduced myocardial energetics of the dystrophic heart Am J Physiol Heart Circ Physiol, published January 22, 2024. DOI: 10.1152/ajpheart.00636.2023
In our latest episode, Associate Editor Dr. Amanda LeBlanc (University of Louisville) interviews author Prof. Pietro Modesti (University of Florence) and expert Dr. Alexandre da Silva (University of Mississippi Medical Center) about the new study by Pellegrino et al. that investigated the pattern of intraventricular hemodynamic forces associated with left ventricular function in women with uncomplicated twin pregnancy. The authors found that, in twin pregnancy, hemodynamic forces misalignment in the first trimester precedes a slight temporary decrease in left ventricular systolic function in the second trimester. In the third trimester, a rightward shift of the end diastolic pressure relationship (EDPR) was, in fact, associated with a realignment of hemodynamic forces and normalization of ventricular contractility indices. Why is twin pregnancy an ideal physiological condition to study increased ventricular workload over time? Listen to this insightful conversation and find out.
Alessio Pellegrino, Loira Toncelli, Lucia Pasquini, Giulia Masini, Federico Mecacci, Gianni Pedrizzetti, and Pietro Amedeo Modesti Left ventricular remodeling in twin pregnancy, noninvasively assessed using hemodynamic forces and pressure-volume relation analysis: prospective, cohort study Am J Physiol Heart Circ Physiol, published January 23, 2024. DOI: 10.1152/ajpheart.00699.2023
Ready Player One? In our latest episode, Dr. Keith Brunt (Dalhousie University) interviews lead author Dr. Joanne DiFrancisco-Donoghue (New York Institute of Technology) and expert Dr. Saurabh Thosar (Oregon Health and Science University Hospital) about a new article published in the AJP-Heart and Circ Call for Papers on Exercise, Physical Activity, and Cardiovascular Health. DiFrancisco-Donoghue et al. raise an important question about the risk for college level e-sport athletes, professionals, and recreational gamers to develop deep vein thromboses. Using Doppler ultrasound recordings of blood flow velocity and volume, the authors found a decrease in both measures when e-sport play was interrupted with a 6-minute walk. DiFrancisco-Donoghue and co-authors found a similar decrease when e-sport athletes wore compression sleeves during play. Could either a break in play for a brief walk or wearing compression stockings help e-sport athletes avoid the risk of deep vein thrombosis caused by prolonged sitting? What effects might this have on executive function, improvement in game play, and for that matter, sleep? If you are a recreational gamer or hoping to go professional, a casual e-sports spectator, or even an active member of the military sitting for prolonged periods of time, you don’t want to miss this engaging and enlightening episode! Listen now.
Joanne DiFrancisco-Donoghue, Kelly Borges, Timothy Li, Olivia Ballone, Hallie Zwibel, and Peter C. Douris Reducing thrombotic risks in video gamers: investigating the benefits of walking and compression sleeves on blood hemodynamics Am J Physiol Heart Circ Physiol, published February 8, 2024. DOI: 10.1152/ajpheart.00669.2023
I Spy Physiology Blog by Erica Roth
How Can Walking and Wearing Socks Help Video Gamers?
What is the relationship between cardiovascular developmental programming and the risk of stroke later in life? Listen as Guest Editor Dr. Helen E. Collins (University of Louisville) interviews author Dr. Nafisa Jadavji (Midwestern University) and expert Dr. Deanne Hryciw (Griffith University) about the latest research by Pull et al. looking at underlying mechanisms associated with a poor-quality diet during pregnancy. One-carbon metabolism is essential for biosynthesis of DNA and proteins, as well as methylation. Jadavji and co-authors demonstrated that maternal dietary deficiency in one-carbon (1C) metabolism, either in folic acid or choline, resulted in reduced cerebral blood flow in adult offspring after an ischemic stroke. Pull et al. focused their investigation on female offspring and identified this effect in 3-month-old offspring but not 11-month-old offspring. The results point to the key role that maternal diet has in early life programming, fetal development, and long-term cerebrovascular health. Are there many downstream pathways that are altered by one-carbon metabolism deficiencies? Is there a negative impact of folic acid over-supplementation? Listen now to find out.
Kasey Pull, Robert Folk, Jeemin Kang, Shaley Jackson, Brikena Gusek, Mitra Esfandiarei, and Nafisa M. Jadavji Impact of maternal dietary folic acid or choline dietary deficiencies on vascular function in young and middle-aged female mouse offspring after ischemic stroke Am J Physiol Heart Circ Physiol, published October 30, 2023. DOI: 10.1152/ajpheart.00502.2023
Given that there appears to be variation in significant risk to the cardiovascular system following SARS-CoV2 infection with regard to age and sex, the latest study by Rouhana et al. provides a foundation for studying sex differences with a preclinical model of infection to the direct exposure to SARS-CoV-2 and the impact on the myocardium of ferrets. Listen as Associate Editor Dr. Keith Brunt (Dalhousie University) interviews authors Dr. Alyson Kelvin (University of Saskatchewan) and Dr. Glen Pyle (University of Guelph) along with expert Dr. Susan Cheng (Cedars-Sinai Smidt Heart Institute). The authors identified that phosphokinase expression, normally associated with cardiac stress remodeling, is distinct by time and sex effects. Additionally, the authors found that inflammatory patterns of macrophage markers showed inherent sex differences in immune responses at the level of the myocardium. Why are ferrets a such a useful preclinical model for understanding SARS-CoV2 infection? How do immune inflammatory responses differ by sex, timing, and age? As Dr. Brunt points out, “There is power in observation, collaboration, and when it comes to bugs and bodies…it’s physiology.” Read the paper, listen to this podcast, and find out more.
Sarah Rouhana, Kathy Jacyniak, Magen E. Francis, Darryl Falzarano, Alyson A. Kelvin, W. Glen Pyle Sex differences in the cardiac stress response following SARS-CoV-2 infection of ferrets Am J Physiol Heart Circ Physiol, published October 18, 2023. DOI: 10.1152/ajpheart.00101.2023
What does a mouse heart have to do with an M&M candy (the regular kind, not the peanut variety)? In our latest episode, Associate Editor Dr. Crystal Ripplinger (University of California, Davis) interviews author Dr. Tim Domeier (University of Missouri) and expert Dr. DeWayne Townsend (University of Minnesota) about the recent study by Haffner et al et al. The authors examined cardiac calcium mishandling and damage in the setting of Duchenne muscular dystrophy (DMD). Using a genetic mouse model of DMD crossed with a mouse that expresses a genetically encoded calcium indicator, Domeier and colleagues investigated changes in intracellular calcium handling in response to increased preload. The unexpected finding was that after the acute preload challenge, many of the cells were missing-in-action. What was going on with these missing cells? Listen as we talk about how individual dystrophic cells blow up if stretched too far, and why pointing microscopes in different directions might be the next step to overcome optical imaging challenges. Don’t miss this episode – the enthusiasm for science, tiny pumping mouse hearts, and squishy cells is contagious!
Vivian Haffner, Zahra Nourian, Erika M. Boerman, Michelle D. Lambert, Laurin M. Hanft, Maike Krenz, Christopher P. Baines, Dongsheng Duan, Kerry S. McDonald, Timothy L. Domeier Calcium handling dysfunction and cardiac damage following acute ventricular preload challenge in the dystrophin-deficient mouse heart Am J Physiol Heart Circ Physiol, published October 18, 2023. DOI: 10.1152/ajpheart.00265.2023
People living with HIV have an increased risk of developing cardiovascular disease, including coronary artery disease. Until now, it has been unclear why. In this episode, Guest Editor Dr. Ashley Walker (University of Oregon) interviews author Dr. Efthymios Ziogos (Johns Hopkins Medicine) and expert Dr. Jennifer Williams (McMaster University) about the recent study by Ziogos et al. published in the Call for Papers Impact of Aging on CV System. Ziogos and co-authors used advanced MRI to assess coronary endothelial function noninvasively and without contrast in order to compare endothelial-dependent vasoreactive responses in coronary arteries to isometric handgrip exercise, both in people living with HIV and HIV negative individuals. The authors found that coronary endothelial function was impaired in people living with HIV, compared to HIV negative individuals. While it is known that there is a negative correlation between age and coronary endothelial function in HIV negative individuals, the authors found no correlation between age and endothelial function in HIV positive individuals, suggesting early vascular aging in individuals with HIV. This study is truly an example of an important research question that went unaddressed until recently because of the need for the advanced measurement techniques used by Ziogos and collaborators. While there is still much to learn about HIV, this research offers new insights into the potential causes of increased coronary artery disease in people living with HIV, and provides new avenues for preventive cardiology research in this population. Listen now to find out more.
Efthymios Ziogos, Yaa A. Kwapong, Robert G. Weiss, Michael Schär, Todd T. Brown, Shashwatee Bagchi, Alborz Soleimanifard, Tarek Harb, Damani A. Piggott, Gary Gerstenblith, Thorsten M. Leucker, Allison G. Hays Coronary Artery Endothelial Function and Aging in People with HIV and HIV-Negative Individuals Am J Physiol Heart Circ Physiol, published October 9, 2023. DOI: 10.1152/ajpheart.00143.2023
What does it sound like when a young researcher meets one of his science heroes for the first time? Listen to this episode of The AJP-Heart and Circ Podcast to find out. Associate Editor Dr. Keith Brunt (Dalhousie University) interviews author Dr. Holger Burchert (University of Basel) and leading expert Dr. William Stringer (Lundquist Institute at Harbor-UCLA Medical Center) about a new Methods and Resources article published by Burchert and Klimpel as part of the recent Call for Papers on Exercise, Physical Activity, and Cardiovascular Health. The article by Burchert et al. is an important contribution of methodological advancement built upon a foundation of established literature, dating back to Fick’s Principle, which first appeared as a two-paragraph conference abstract published in German in 1870 and later translated by The New England Journal of Medicine in 1948. Fick was the first to realize that cardiac output is equal to oxygen consumption divided by the arterial mixed venous oxygen content difference, allowing the first accurate determination of cardiac output. While non-invasive measurements of oxygen consumption and heart rate are now routine, sampling arterial and mixed venous blood is inherently challenging. This makes finding non-invasive techniques for these measurements incredibly important. Enter the OG of the linear method for determining the arterial mixed venous oxygen content difference, Dr. William Stringer. In his seminal 1997 article published in the Journal of Applied Physiology, “Cardiac output estimated noninvasively from oxygen uptake during exercise”, Dr. Stringer found that the arterial mixed venous oxygen content difference during incremental exercise can be estimated because it behaves in a predictable, linear fashion, thus avoiding the difficult blood sampling. Reading the article by Stringer et al., which was referenced in the CPET (cardiopulmonary exercise testing) machine manual Burchert used during his PhD work, sparked Burchert’s interest to investigate the literature and ultimately build on Stringer’s methodological approach by collaborating with this former school friend Dr. Fabian Klimpel. Burchert et al. found that a 3rd order polynomial S-curve described the arterial mixed venous oxygen content difference slightly better. More importantly, the authors also determined that the inflection point of this function could be related to the first ventilatory threshold and the inflection point of the oxygen dissociation curve. Why is this important? A deeper understanding of the mechanisms behind the s-shaped response has potential clinical translation, as the method could be further developed by tailoring it to individual patients. Listen as we discuss why it is important for early career researchers “to look back in order to look forward,” to use collaborators from other disciplines to support thinking creatively about cardiovascular physiology, and to align with mentors who facilitate young careers through constructive peer review and publication.
Holger Burchert and Fabian Klimpel Revisiting cardiac output estimated noninvasively from oxygen uptake during exercise: an exploratory hypothesis-generating replication study Am J Physiol Heart Circ Physiol, published August 25, 2023. DOI: 10.1152/ajpheart.00330.2023
William W. Stringer, James E. Hansen, and K. Wasserman Cardiac output estimated noninvasively from oxygen uptake during exercise J Appl Physiol, published March 1, 1997. DOI: 10.1152/jappl.1997.82.3.908
Fick, A On the Measurement of the Blood Quantum in the Ventricles of the Heart. Bauhaus-Universität Weimar, 1870, p. 16.
Come for the yoga metaphors, stay for the science. In this episode, Associate Editor Dr. Keith Brunt (Dalhousie University) interviews author Dr. Stacy Hunter (Texas State University) and expert Dr. Annet Kirabo (Vanderbilt University) about the new study by Hunter et al., which examined the impact of hot yoga on sodium-induced pressor responses and endothelial function of Black women. In a randomized control trial that combined the thermal stress of hot yoga and a salt challenge, the authors investigated human homeostatic regulation in terms of whole-body physiology, cardiorenal responses, physical activity, and the exercise environment. In their study, Hunter and collaborators controlled for sodium intake by separating participants into high and low sodium groups, with pre and post analyses of body mass, ambulatory blood pressure, urinalysis, and flow mediated dilation. The authors found that participants who actively engaged in hot yoga showed increased flow mediated dilation but not increased blood pressure. Why did the authors use a 3-day, not 5-day, hot yoga exercise protocol? What insights can be gained about salt-sensitivity in Black women from this study, which incorporated a form of exercise that activated both thermoregulation and the parasympathetic nervous system? Listen to find out.
Stacy D. Hunter, Stavros A. Kavouras, and Mitra Rahimi Exploring heated exercise as a means of preventing the deleterious effects of high-sodium intake in Black women Am J Physiol Heart Circ Physiol, published May 4, 2023. DOI: 10.1152/ajpheart.00699.2022
What is the impact of female sex hormones on obesity, diabetes, and vascular dysfunction? In this episode, Deputy Editor Dr. Zam Kassiri (University of Alberta) interviews authors Dr. Bruna Visniauskas and Dr. Minolfa Prieto (both at Tulane University School of Medicine), along with expert Dr. Glen Pyle (IMPART Network at Dalhousie Medicine) about the new study by Visniauskas et al. Using a long-term high fat diet mouse model of type 2 diabetes, the authors found that male mice had higher increases in plasma levels of prorenin and renin soluble prorenin receptor and angiotensin 2, which was also associated with hypertension and carotid artery stiffness, compared to female mice. This led Visniauskas et al. to interrogate a potential causal role of soluble prorenin receptor in development of the diabetes phenotype in the mice fed the high fat diet. Since female mice were less prone to the diabetic phenotype than males, the authors ovariectomized female mice to interrogate the role of estrogen in the development of the diabetes phenotype. Prieto, Visniauskas, and co-authors observed the Type 2 diabetes phenotype in both males and ovariectomized females but not intact females. How does dipping vs. non-dipping hypertension factor in? Will the soluble prorenin receptor emerge as a more reliable biomarker for vascular pathologies related to diabetes? Listen and find out.
Bruna Visniauskas, Virginia Reverte, Caleb M. Abshire, Benard O. Ogola, Carla B. Rosales, Michelle Galeas-Pena, Venkata N. Sure, Siva S. V. P. Sakamuri, Nicholas R. Harris, Isabella Kilanowski-Doroh, Alexandra B. Mcnally, Alec C. Horton, Margaret Zimmerman, Prasad V. G. Katakam, Sarah H. Lindsey, and Minolfa C. Prieto High-plasma soluble prorenin receptor is associated with vascular damage in male, but not female, mice fed a high-fat diet Am J Physiol Heart Circ Physiol, published April 25, 2023. DOI: 10.1152/ajpheart.00638.2022
When is it safe to have surgery after COVID? Listen as Associate Editor Dr. Jason Carter (Baylor University) interviews lead author Dr. Anai Kothari (Medical College of Wisconsin) and leading expert Dr. Michael Joyner (Mayo Clinic) about the groundbreaking new research study by SenthilKumar et al. that evaluated how pre-operative COVID infection might affect a patient’s risk of post-operative major adverse cardiovascular and cerebrovascular events (MACE) by analyzing. data from 457,804 patients within the National COVID Cohort Collaborative (N3C) Data Enclave. In fact, it was a surgical operation in October 2020 that inspired Kothari and collaborators to consider how the stress of surgery combined with the potential end-organ changes that happen with prior COVID infection would impact surgical outcomes. If patients had a prior history of COVID followed by a subsequent non-emergency surgery, the authors found a 12% increase in overall risk of having a major adverse cardiovascular or cerebrovascular event after surgery. The authors found that most patients had surgery more than 8 weeks after COVID infection. However, if patients had surgery in the first 4 weeks after COVID infection, there was a slight increase in number of post-surgical MACE. Disease severity had a major impact on post-surgerical (surgical) incidence of MACE. In contrast, vaccination against COVID decreased the risk of MACE without increasing the risk of any post-operative negative outcomes the group assessed. Listen as these experts discuss surgical timing and the role of COVID vaccines to not only reduce risk of post-surgical MACE for surgical patients but also protect immunocompromised individuals in the greater population.
Gopika SenthilKumar, Nathaniel B. Verhagen, Salma A. Sheriff, Xin Yang, Carlos E. Figueroa Castro, Aniko Szabo, Brad W. Taylor, Njeri Wainaina, Kathryn Lauer, Jon C. Gould, and Anai N. Kothari;on behalf of the N3C Consortium Preoperative SARS-CoV-2 infection increases risk of early postoperative cardiovascular complications following noncardiac surgery Am J Physiol Heart Circ Physiol, published April 25, 2023. DOI: 10.1152/ajpheart.00097.2023
What does being a good ally look like? In a new Perspective, authors Dr. Karla Haack (Merck), Dr. Austin Robinson (Auburn University), Dr. Dexter Lee (Howard University College of Medicine), Dr. Keisa Mathis (University of North Texas Health Science Center), and Dr. Junie Paula Warrington (University of Mississippi Medical Center) discuss how the American Physiological Society (APS) can promote Black physiologists and support them in the challenges they face. The authors sat down with The AJP-Heart and Circ Podcast for a wide-ranging interview at the cross-section of social justice and science. The authors feel that APS has a unique opportunity as an international organization to be at the forefront of supporting Black physiologists and boosting the success of underrepresented minority APS members. As the authors note, Black students are often first-generation college students, and therefore mentoring and K-12 physiology outreach are critically important. Robinson et al. discuss issues around the underrepresentation of Black physiologists at the faculty level, as well as challenges with access to pilot funding to support Black early career researchers. The authors discuss many actionable steps, such as inviting Black physiologists to be scientific co-investigators and co-authors on studies, as well as partnering with Historically Black Colleges and Universities to help build a pipeline of future Black physiologists. The authors take-home message? Don’t underestimate the power of being an ally and using your voice to amplify the voices of Black physiologists. As Dr. Junie Paula Warrington stated, “One person at a time, we can make a huge impact.”
Austin T. Robinson, Nathaniel D. M. Jenkins, Sofia O. Sanchez, Karla K. V. Haack, Dexter L. Lee, Keisa W. Mathis, and Junie P. Warrington Supporting and promoting Black physiologists: how can the APS help? Am J Physiol Heart Circ Physiol, published May 4, 2023. DOI: 10.1152/ajpheart.00082.2023
How can researchers capture the most accurate demographic data possible on intake surveys for human participant studies? Listen as author and moderator Dr. Karla Haack (Merck) interviews co-authors Dr. Jesse Moreira (Boston University) and Dr. Troy Roepke (Rutgers, The State University of New Jersey) about their recent Perspective regarding how researchers can do inclusive and precise research with an open mindset in order to avoid excluding groups of people when developing survey demographic questions for human participant research studies. In their article, Moreira et al. offer actionable steps to develop inclusive survey language for the LGBTQIA2S+ community with precise science at the forefront. The goal is to increase participation among LGBTQIA2S+ people and collect demographic data in a manner that does not alienate or marginalize anyone who may already be experiencing marginalization. The authors make the case that researchers should not be afraid to be precise, and careful attention to language does not involve extra effort on the part of researchers. For example, researchers can include a semi-exhaustive list of gender along with a fill-in “I self-describe as" field. If researchers introduce themselves using their own preferred pronouns, the authors explained, and then ask what pronouns study participants prefer to use, it can make an enormous difference to the sense of belonging for potential study participants. Words help science to be more exact. Simply stated, words matter. Listen to learn more.
Jesse D. Moreira, Karla Haack, Vee White, Melissa L. Bates, Deepa M. Gopal, and Troy A. Roepke Importance of survey demographic questions to foster inclusion in medicine and research and reduce health inequities for LGBTQIA2S+ individuals Am J Physiol Heart Circ Physiol, published May 12, 2023. DOI: 10.1152/ajpheart.00152.2023
Heart failure with preserved ejection fraction (HFpEF) is, in many ways, a fascinating tale of modern cardiovascular medicine that, according to lead author Dr. Joshua Hare (University of Miami Miller School of Medicine), has taught cardiovascular researchers and clinicians a lot of humility. Understanding HFpEF in a variety of animal models has led to a paradigm shift away from heart failure linked to low ejection fraction. In this episode Associate Editor Dr. Jonathan Kirk (Loyola University Chicago Stritch School of Medicine) interviews Dr. Hare along with expert Dr. Julie McMullen (Baker Heart and Diabetes Institute, Melbourne, Australia) about the latest study by Kanashiro-Takeuchi et al. The Hare Lab was originally attracted to a cardiometabolic model of HFpEF pioneered by Dr. Joseph Hill, because in a large proportion of human patients, HFpEF is due to metabolic syndrome, which is a combination of obesity, diabetes, and hypertension. Armed with the ability to create this cardiometabolic HFpEF model, Hare and co-authors decided to test growth hormone-releasing hormone-agonist using a powerhouse of methods to determine if exercise intolerance could be improved. Kanashiro-Takeuchi et al. found that diastolic function and exercise performance improved, and myocyte hypertrophy and fibrosis were restored. Essentially all of the features of cardiometabolic HFpEF responded to treatment with GHRH-agonist. The authors did not see a reduction in blood pressure or weight, indicating a direct myocardial effect. In a wide-ranging discussion that touches on skeletal muscle, aging, sarcomeric proteins, and the technical complexities of running titin gels and PV loops, our experts explain why HFpEF is such a challenging syndrome to treat and why this translational research is so important. Listen now.
Rosemeire M. Kanashiro-Takeuchi, Lauro M. Takeuchi, Raul A. Dulce, Katarzyna Kazmierczak, Wayne Balkan, Renzhi Cai, Wei Sha, Andrew V. Schally, Joshua M. Hare Efficacy of a Growth Hormone-Releasing Hormone Agonist in a Murine Model of Cardiometabolic Heart Failure with Preserved Ejection Fraction Am J Physiol Heart Circ Physiol, published April 25, 2023. DOI: 10.1152/ajpheart.00601.2022.
“You cannot make good predictions for patients until you understand the physiology,” stated Dr. Kristian Becker (Icahn School of Medicine at Mount Sinai). Becker and co-authors demonstrated for the first time echocardiographic evidence of a transition in the left ventricular vortex patterns of the heart from the newborn period to the adult period. Listen as Associate Editor Dr. Amanda LeBlanc (University of Louisville) interviews Dr. Becker and expert Dr. Ann Chiao (Oklahoma Medical Research Foundation) about how the authors used vector flow mapping to identify changes in cardiovascular efficiency, which were marked by increased energy loss during infancy. In this Rapid Report, which was published in the Call for Papers on the Impact of Aging in the Cardiovascular System, Becker and co-authors found that one early diastolic vortex in newborns transitions to two early diastolic vortices by 2 years of age. Vector flow mapping is an echocardiographic technique that combines doppler ultrasound and blood speckle tracking to follow the direction and velocity of blood in the heart. As a bridge between cardiac MRI and traditional ultrasound, vector flow mapping gives researchers and pediatric cardiologists an understanding of how blood is flowing in the heart and whether heart defects or cardiomyopathies affect blood flow. Given that the heart is a master adapter—it grows from about the size of a walnut at birth to the size of a peach in adulthood—mapping energy loss when the heart is transitioning in size and shape with age is critically important to clinicians. The authors want to take their research from bench to bedside, and back to the bench, for a complete understanding of the heart. Listen now to find out more.
Kristian C. Becker, Jennifer Cohen, Jon D. Nyce, Jen Lie Yau, Santosh C. Uppu, Partho P Sangupta, and Shubhika Srivastava Age Related Changes in Left Ventricular Vortex and Energy Loss Patterns: From Newborns to Adults Am J Physiol Heart Circ Physiol, published March 10, 2023. DOI: 10.1152/ajpheart.00002.2023
While anxiety disorders are the most common mental health issue in the United States and are known to increase the risk of hypertension and cardiovascular disease, the links between anxiety, muscle sympathetic nerve activity and blood pressure have not been interrogated to date. Listen as host Dr. Megan Wenner (University of Delaware) interviews author Dr. Jeremy Bigalke (Montana State University) and expert Dr. Jody Greaney (The University of Texas at Arlington) about the latest research by Bigalke et al. Leveraging a large dataset of 88 young adults, the authors examined the relationship between anxiety, blood pressure and resting muscle sympathetic nerve activity using seated blood pressure measurements and the Spielberger State/Trait Anxiety Inventory, which denotes an individual’s propensity for anxiousness along a spectrum. After controlling for several key characteristics including age and sex, Bigalke and collaborators determined that there was a modest relationship between anxiety symptom severity and resting sympathetic outflow in young otherwise healthy adults. Do these changes in sympathetic regulation of blood pressure indicate a significantly increased long-term risk for cardiovascular comorbidities later in life? Our experts discuss this work in the context of the dramatic increase in patients diagnosed with anxiety and associated mental health disorders during the COVID pandemic, and delve into the consideration of sex as a biological variable in the prevalence of anxiety diagnoses among women compared with men. Why are multi-center collaborations critical to the future of research linking subjective psychological characteristics to physiological outcomes? Listen and find out.
Jeremy A. Bigalke, John J. Durocher, Ian M. Greenlund, Manda Keller-Ross, and Jason R. Carter Blood pressure and muscle sympathetic nerve activity are associated with trait anxiety in humans Am J Physiol Heart Circ Physiol, published February 17, 2023. DOI: 10.1152/ajpheart.00026.2023
What effects do COVID symptomology and time since diagnosis have on cardiac autonomic function? Listen as Guest Editor Dr. Tiago Peçanha (Manchester Metropolitan University) interviews first author Dr. Rachel Skow (The University of Texas at Arlington) and expert Dr. Chris Minson (University of Oregon) about the research by Skow et al, aimed at better understanding the mechanisms underlying increased cardiovascular risk associated with COVID infection. Skow and co-authors set out to study the cardiovascular health of young adults diagnosed during the early variants of COVID-19 compared to those who had never had COVID. The authors measured resting cardiac baroreflex sensitivity and heart rate variability in order to determine whether having COVID impacted these measures of cardiac autonomic function. Their results were very encouraging: Skow et al. did not show an impact of COVID-19 on cardiac baroreflex sensitivity nor heart rate variability. The authors also studied the impact of symptomology by stratifying their study participants with COVID into different groups – comparing those with persistent symptoms at the time of their assessment to those who did not have persistent symptoms. The authors found no difference between these groups on markers of cardiac autonomic function. However, when Skow and co-authors analyzed their COVID participant group according to date of diagnosis, the authors found better cardiac autonomic function in participants who were studied after a longer time since diagnosis had elapsed, indicating a potential transient effect on cardiac autonomic function in these otherwise healthy young adults. Listen as we discuss the need to study more subjects overall, particularly more diverse patient populations especially in terms of age and co-morbidities, in order to better understand the time course of cardiovascular and autonomic dysregulation during and after COVID.
Rachel J. Skow, Nicole A. Garza, Damsara Nandadeva, Brandi Y. Stephens, Alexis N. Wright, Ann-Katrin Grotle, Benjamin E. Young and Paul J. Fadel Impact of COVID-19 on cardiac autonomic function in healthy young adults: potential role of symptomatology and time since diagnosis Am J Physiol Heart Circ Physiol, published November 21, 2022. DOI: 10.1152/ajpheart.00520.2022
What happens when your hypothesis is…wrong? Listen as host Dr. Dan Tyrrell (University of Michigan Medical School) interviews lead author Dr. Julie Freed (Medical College of Wisconsin) and content expert Dr. Chi Fung Lee (Oklahoma Medical Research Foundation) about the new Rapid Report by SenthilKumar et al., which investigated the function of estradiol on human microvessels. In contrast to their hypothesis, Freed and co-authors found that exogenous estradiol treatment of arterioles isolated from both young and older women promoted endothelial dysfunction. In addition, the authors found that estradiol treatment of microvessels isolated from men led to endothelial and smooth muscle dysfunction. The timing of this article is key, given the new AJP-Heart and Circ requirements launched in January 2023 for considering sex as a biological variable. Freed and collaborators originally hypothesized that estrogen may activate the enzyme sphingosine kinase, and therefore mediate cardioprotective effects in the vasculature. However, that was not the case. Freed summed up their surprising results: “There is something going on here. Do we have all the answers yet? No. But we’re going to figure this out.” Listen as we discuss the complexities of human tissue banking, and the grit and flexibility necessary for all researchers to follow the science where it leads.
Gopika SenthilKumar, Boran Katunaric, Henry Bordas-Murphy, Micaela Young, Erin L. Doren, Mary E. Schulz, Michael E. Widlansky, and Julie K. Freed 17β-Estradiol Promotes Sex-Specific Dysfunction in Isolated Human Arterioles Am J Physiol Heart Circ Physiol, published January 6, 2023. DOI: 10.1152/ajpheart.00708.2022
Is inflammation the driving force for diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF)? In this episode, Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) interviews author Dr. Thassio Mesquita (Cedars-Sinai Medical Center) and expert Dr. Darryl Davis (University of Ottawa Heart Institute) about the research by de Couto et al. Using a Dahl salt-sensitive rat model of HFpEF, the authors delivered cardiosphere-derived cells (CDCs) via intracoronary injection into the microcirculation. After 2 weeks of treatment with CDCs, the hypertensive rats showed improved endothelial-dependent vasodilation, reduced oxidative stress, restored expression of endothelial nitric oxide synthase, and reduced inflammation. Overall, the authors found that CDCs made significant improvements in the cardiovascular health of hypertensive rats with HFpEF. What is the therapeutic potential of cardiospere-derived cells for treating heart failure with preserved ejection fraction (HFpEF)? Listen and learn more.
Geoffrey de Couto, Thassio Mesquita, Xiaokang Wu, Alex Rajewski, Feng Huang, Akbarshakh Akhmerov, Na Na, Di Wu, Yizhou Wang, Liang Li, My Tran, Peter Kilfoil, Eugenio Cingolani, and Eduardo Marbán Cell therapy attenuates endothelial dysfunction in hypertensive rats with heart failure and preserved ejection fraction Am J Physiol Heart Circ Physiol, published October 17, 2022. DOI: 10.1152/ajpheart.00287.2022
The world of cardiac electrophysiology can be daunting, so we suggest that you listen to this insightful conversation with the experts. Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) interviews authors Dr. Crystal Ripplinger (University of California Davis), Dr. Nikki Posnack (The George Washington University and Children's National Hospital), Dr. Alexey Glukhov (University of Wisconsin-Madison), Dr. Matthew Kay (The George Washington University), Dr. Carol Ann Remme (Amsterdam University Medical Centers), and Dr. Alex Quinn (Dalhousie University) about their comprehensive new guidelines for assessment of cardiac electrophysiology and arrhythmias in small animals. This thorough guidelines article by Ripplinger et al. covers many common electrophysiology approaches used in the field at the tissue level, whole heart level, and in vivo measurements. In addition, the authors dive into what parameters investigators may want to measure, providing helpful and clear guidance on how to calculate such parameters and what those parameters might mean in terms of electrophysiology remodeling and arrhythmia propensity. Both senior investigators and trainees will find these guidelines approachable and useful. Listen and learn from the experts.
Crystal M. Ripplinger, Alexey V. Glukhov, Matthew W. Kay, Bastiaan J. Boukens, Nipavan Chiamvimonvat, Brian P. Delisle, Larissa Fabritz, Thomas J. Hund, Bjorn C. Knollmann, Na Li, Katherine T. Murray, Steven Poelzing, T. Alexander Quinn, Carol Ann Remme, Stacey L. Rentschler, Robert A. Rose, and Nikki G. Posnack Guidelines for assessment of cardiac electrophysiology and arrhythmias in small animals Am J Physiol Heart Circ Physiol, published November 21, 2022. DOI: 10.1152/ajpheart.00369.2022.
Is a pre-treatment with low dose cyclosporine immunosuppression necessary to limit allogeneic cardiosphere-derived cell therapy rejection? Listen as Associate Editor Dr. Amanda LeBlanc (University of Louisville) interviews senior author Dr. John Canty (University of Buffalo) and expert Dr. Fabio Recchia (Scuola Superiore Sant'Anna; Temple University) about the latest study by Techiryan et al. In this blinded randomized controlled trial using swine, the authors tested whether low dose cyclosporine could be initiated at the time of reperfusion. In contrast to previous studies, the authors were not able to reproduce the cardioprotective effects demonstrated by allogeneic CDCs without cyclosporine. Conducting large animal studies is like conducting an orchestra, with many members of the lab playing specific roles. What is it like to take a pig with a balloon occluder in their anterior descending artery 100 yards down the hall to the imaging center for a CT scan while the animal is having an acute infarction? Listen as we discuss the challenges of blinded preclinical studies and how large animal studies can offer unique preclinical insights that may translate more effectively to clinical treatment of cardiovascular disease.
George Techiryan, Brian R. Weil, Rebeccah F. Young, and John M. Canty Jr. Widespread intracoronary allogeneic cardiosphere-derived cell therapy with and without cyclosporine in reperfused myocardial infarction Am J Physiol Heart Circ Physiol, published October 17, 2022. DOI: 10.1152/ajpheart.00373.2022
When Dr. Ashley Walker (University of Oregon) began to study sex differences with vascular aging and cognitive decline, she and her team went to the literature for guidance on research study design to account for the confounding variable of estrous cycle in young female mice. Problem: There were no recommendations in the literature. Solution: The Walker Lab got to work. In our latest episode, Dr. Amanda LeBlanc (University of Louisville) interviews lead author Dr. Ashley Walker and first author Ms. Mackenzie Kehmeier (University of Oregon), along with expert Dr. Sarah Lindsey (Tulane University) about the novel study by Kehmeier et al. – the first of its kind – to show that the impact of estrogen on vascular stiffness changes with each day of the female mouse estrous cycle. The authors found that estrous phase was associated with lower in vivo large artery stiffness in mice, but ex vivo resistance artery endothelial function was not different between estrous cycle phases. Kehmeier et al. determined that estrogen receptor expression is modulated by the estrous cycle in an artery dependent manner, which means that estrous cycle phase in young female mice should be considered when measuring in vivo arterial stiffness. What techniques do the authors recommend for other investigators to best determine accurate staging of the estrous cycle? Listen to find out.
Mackenzie N. Kehmeier, Bradley R. Bedell, Abigail E. Cullen, Aleena Khurana, Holly J. D’Amico, Grant D. Henson, Ashley E. Walker In vivo arterial stiffness, but not isolated artery endothelial function, varies with the mouse estrous cycle Am J Physiol Heart Circ Physiol, published October 14, 2022. DOI: 10.1152/ajpheart.00369.2022
Have you ever had an experimental design deviate from expectations? Well, this episode is for you. Associate Editor Dr. Keith Brunt (Dalhousie University) interviews Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) about her recently published article by Hu et al., along with content expert Dr. Joshua Man ( Tufts Medical Center), to discuss how unexpected results and negative findings can, in and of themselves, lead to new discoveries. Kassiri and co-authors used a Cre/lox system to study the role of disintegrin and metalloproteinase-17 (Adam17) in smooth muscle cells (SMC) in a mouse model of atherosclerosis. LDL-deficient mice that consumed a high fat diet had normal skin. However, mice with floxed alleles of Adam17 driven by Sm22alpha developed severe skin lesions. The loss of gene function and Sm22alpha expression was apparent in keratinocytes. Adam17 deletion by a different SMC driver, Myh11-Cre, did not result in skin lesions in the same atherosclerosis model. Staying true to the expression that experience is what you get when you don’t get what you want, Hu et al. published their results in the hopes of helping other labs and animal care & use committees avoid similar pitfalls. What are the potential ramifications for cardiovascular researchers, keratinocyte biologists, and dermatologists? Listen and find out.
Mei Hu, Sho Hiroyasu, David J. Granville, Zamaneh Kassiri Implications of Sm22alpha-Cre expression in keratinocytes and unanticipated inflammatory skin lesion in a model of atherosclerosis Am J Physiol Heart Circ Physiol, published August 31, 2022. DOI: 10.1152/ajpheart.00325.2022
Why do many severe COVID-19 survivors experience exercise intolerance as a lingering consequence of their viral infection? In this episode, Guest Editor Dr. Tiago Peçanha (Manchester Metropolitan University) interviewed lead author Dr. Hamilton Roschel (University of Sao Paulo) and expert Dr. John Durocher (Purdue University Northwest) about the latest study by Longobardi et al., which investigated the impact of previous severe COVID-19 infection on cardiorespiratory responses to a maximal exercise test. The authors enrolled survivors of severe COVID-19 who had previously been admitted to an intensive care unit during the acute phase of their illness in this cross-sectional study within a randomized controlled trial. The authors found that VO2 kinetics were significantly impaired at the onset and recovery phases of the exercise protocol in the COVID survivors. What do these experts think about the central and peripheral factors underlying the exertional intolerance and chronotropic incompetence in COVID survivors? Listen now.
Igor Longobardi, Danilo Marcelo Leite do Prado, Karla Fabiana Goessler, Matheus Molina Meletti, Gersiel Nascimento de Oliveira Júnior, Danieli Castro Oliveira de Andrade, Bruno Gualano, Hamilton Roschel Oxygen uptake kinetics and chronotropic responses to exercise are impaired in survivors of severe COVID-19 Am J Physiol Heart Circ Physiol, published September 2, 2022. DOI: 10.1152/ajpheart.00291.2022
In our latest episode of Behind the Bench from AJP-Heart and Circ, co-hosts Dr. Tommy Martin and Dr. Charlotte Usselman interview bioengineer and first author Dr. Amy Garrett. Dr. Garrett joined the Auckland Bioengineering Institute in 2016, where she completed a Masters in Engineering followed by a PhD. After joining the cardiac energetics group for her post-doc, Dr. Garrett embarked on a research journey tackling the development of the Windkessel loading system for work-loop contractions. What’s that, you’re wondering? The work-loop calorimeter is an experimental device fine-tuned by the Auckland Bioengineering Institute over the past 20 years. The device performs stress-length work-loops on cardiac trabeculae. It is both fascinating and complicated. Good news: Dr. Garrett explains everything! Find out more about her scientific journey, and why Windkessel loaded loops are important. Listen now.
Amy S. Garrett, Denis S. Loiselle, Andrew J. Taberner, June-Chiew Han Slower shortening kinetics of cardiac muscle performing Windkessel work-loops increase mechanical efficiency Am J Physiol Heart Circ Physiol, published August 31, 2022. DOI: 10.1152/ajpheart.00074.2022
What is a cytokine storm in COVID-19 patients and how does it adversely affect organ systems in diabetes patients? In our latest episode, Associate Editor Dr. Keith Brunt (Dalhousie University) interviews lead author Dr. Dinender Singla (University of Central Florida) and expert Dr. Mark Chappell (Wake Forest University) about the new Review by Narasimhulu and Singla on the pathophysiology of the SARS-CoV2 virus as it relates to diabetes. As we now know, the virus enters cells through the angiotensin converting enzyme 2 receptors, which is especially concerning for patients with pre-existing cardiovascular complications and co-morbidities such as diabetes, given that renin-angiotensin system is a driving force of cardiovascular disease. In this insightful and wide-ranging interview, our experts discuss viral variance, sex differences, the need for more sophisticated pre-clinical models, long COVID, and implications for co-morbidity management. Where does the field go from here? Read, listen, learn.
Chandrakala Aluganti Narasimhulu and Dinender K. Singla Mechanisms of COVID-19 pathogenesis in diabetes Am J Physiol Heart Circ Physiol, published August 4, 2022. DOI: 10.1152/ajpheart.00204.2022
How do the 3 Rs of Research – Refinement, Reduction, Replacement – factor into a methodological paper regarding a novel quantitative method for using an electrocardiogram to determine which animals have infarcts that reflect successful coronary ligation? Listen as Consulting Editor Dr. Ganesh Halade (University of South Florida) interviews lead author and Consulting Editor Dr. Kristine DeLeon-Pennell (Medical University of South Carolina) and content expert Dr. Corey Reynolds (Merck) about the recent work by Broughton et al. What started as an internal project to improve The DeLeon-Pennell Lab’s surgical success grew into a research article published as part of a Call for Papers on Innovation in Improving Rigor and Reproducibility in Cardiovascular Research. The DeLeon-Pennell Lab was interested in streamlining infarct size between lab members, students, and technicians during the surgical procedures used for their mouse studies. Aiming for a threshold of 35% infarct size, the DeLeon-Pennell Lab wanted to move beyond looking only at the elevation of the T wave to confirm infarct size. To do so, Broughton et al. designed a new ECG method that provides real-time feedback during the procedure. Broughton et al. found that area under the QRS curve is stronger for predicting successful MI surgeries with an infarct size greater than 35%. This new method will ultimately allow researchers to reduce the time spent performing surgical experiments and the overall number of animals used. Listen now to find out more.
Philip Broughton, Miguel Troncoso, Alexa Corker, Alexus Williams, Dawson Bolus, Gualberto Munoz, Caroline McWhorter, Hallie Roerden, Penny Huebsch, and Kristine Y. DeLeon-Pennell Riding the wave: a quantitative report of electrocardiogram utilization for myocardial infarction confirmation Am J Physiol Heart Circ Physiol, published August 3, 2022. DOI: doi.org/10.1152/ajpheart.00201.2022
Is it bad for our cardiovascular health to “spring forward” into Daylight Saving Time? On March 15, 2022, the U.S. Senate passed the Sunshine Protection Act, which aims to make Daylight Saving Time permanent and eliminate bi-annual seasonal clock changes in the spring and fall. In this episode, Consulting Editor Dr. Austin Robinson (Auburn University) interviews lead author and Associate Editor Dr. Jason Carter (Montana State University) and expert Dr. Josiane Broussard (Colorado State University) about a Perspective by Carter et al. which unpacks the negative impacts on overall cardiovascular health, as well as the increased risks of adverse cardiovascular events associated with changing our clocks between Standard Time and Daylight Saving Time. While the proposed Sunshine Protection Act legislation appears to offer a solution—instituting Daylight Saving Time as the permanent time – both the American Academy of Sleep Medicine and the Society for Research on Biological Rhythms argue that the healthier choice is Standard Time. Studies have shown that the shift to Daylight Saving Time results in increased incidence of myocardial infarction, stroke, and hospital admissions attributed to atrial fibrillation. In addition, the decrease in morning light with Daylight Saving Time has potential adverse effects on mental health, because morning sunshine plays a critical role in synchronizing our internal clocks to avoid circadian misalignment. Could shifting 30 minutes rather than 60 minutes be a reasonable compromise? Listen now to find out.
Jason R. Carter, Kristen L. Knutson, Babak Mokhlesi Taking to “heart” the proposed legislation for permanent daylight saving time Am J Physiol Heart Circ Physiol, published June 13, 2022. DOI: doi.org/10.1152/ajpheart.00218.2022
The eyes are the window to the soul, as the old saying goes, but are the eyes also the window to cardiovascular disease? Diabetic retinopathy is a common diabetic microvascular disease and a leading cause of blindness in diabetes patients worldwide. Defects in the blood-retinal barrier caused by increased production of vascular endothelial growth factor-A isoforms promote angiogenesis and permeability. Listen as Consulting Editor Dr. Shawn Bender (University of Missouri, Columbia) interviews first author Dr. Naseeb Malhi (City of Hope National Medical Center), senior author Dr. David Bates (University of Nottingham), and expert Dr. Jerome Breslin (University of South Florida) about the new study by Malhi et al, which investigated whether serine-arginine-rich protein kinase-1 (SRPK1) inhibition can attenuate the pathophysiology of diabetic retinopathy. The authors conducted a combination of mechanistic in vitro studies using human retinal pigment epithelial cells and studies in type 1 diabetic rats to investigate whether SRPK1 is activated in diabetes, and whether an SRPK1 inhibitor (SPHINX31) switches VEGF splicing in diabetic retinopathy to prevent increased vascular permeability into the retina. The novel intervention design of delivering the SRPK1 inhibitor via eyedrop in the authors’ diabetic rat model was used preventatively at the outset of the diabetes phenotype. Does this unique treatment modality offer promise for treating established diabetic retinopathy? Listen and learn.
Naseeb K. Malhi, Claire L. Allen, Elizabeth Stewart, Katherine L. Horton, Federica Riu, Jennifer Batson, Winfried Amoaku, Jonathan C. Morris, Kenton P. Arkill, David O. Bates Serine-arginine-rich protein kinase-1 inhibition for the treatment of diabetic retinopathy Am J Physiol Heart Circ Physiol, published May 10, 2022. DOI: 10.1152/ajpheart.00001.2022
This episode of Behind the Bench with AJP-Heart and Circ is full of connections. Returning co-host Dr. Charlotte Usselman is joined by her new co-host Dr. Tommy Martin. We first met Tommy when we interviewed him last year for Behind the Bench episode 10 as a trainee in the lab of AJP-Heart and Circ Associate Editor Dr. Jonathan Kirk. Jonathan was the original co-host of Behind the Bench along with Dr. Lisandra de Castro Brás. Speaking of Jonathan and Lis… big shout out to the original Behind the Bench co-hosts for their stellar insights and witty humor! Fast forward to the proverbial passing of the Behind the Bench microphone to Charlotte and Tommy and their wide-ranging interview with Dr. Jody Greaney, lead author of a new study interrogating vascular dysfunction as one mechanism, of the many potential mechanisms, linking major depressive disorder to CV disease risk. Greaney and co-authors investigated upstream mechanisms of vascular dysfunction and increased vascular superoxide by targeting inflammation with short-term salicylate treatment in a young adult population with major depressive disorder and found that this treatment did improve microvascular endothelium-dependent dilation. Listen as Jody discusses how she persevered with her small proof-of-concept study through finishing her post-doc, obtaining a faculty position, navigating the start-up her own lab, pandemic related interruptions to basic research, and peer reviewer comments that seemed daunting to overcome. Could depression, at its core, be characterized as an inflammatory disease? Are you at a critical career fork in the road and need some insight? Listen now.
Jody L. Greaney, Erika F. H. Saunders, Lacy M. Alexander Short-term salicylate treatment improves microvascular endothelium-dependent dilation in young adults with major depressive disorder
Am J Physiol Heart Circ Physiol, published April 14, 2022. DOI: 10.1152/ajpheart.00643.2021
First, a thank you to frontline healthcare workers, clinical researchers, and one determined master’s student Michelle Cristina-Oliveira of the Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo for their bravery and dedication to science and medicine! In this episode we bring you a conversation between Associate Editor Dr. Jason Carter (Montana State University), lead author Dr. Tiago Pecanha (Universidade de São Paulo, and Manchester Metropolitan University), and expert Dr. Paul Fadel (The University of Texas at Arlington). From June 2020 to May 2021 first author Michelle Cristina-Oliveira screened over 600 patients at the height of the COVID-19 pandemic in São Paulo, Brazil in order to enroll 211 COVID-19 patients within 72 hours of hospital admission. The authors sought to determine whether brachial artery flow-mediated dilation and carotid intima-media thickness measured upon hospital admission were associated with acute outcomes in hospitalized COVID-19 patients. Based on initial case reports, Cristina-Oliveira et al. felt that the endothelium could be an important target for SARS-CoV2. The authors hypothesized that measuring markers of endothelial function and atherosclerosis upon hospital admission could provide critically important information about potential risks of mortality, admission to ICU, and requirement for mechanical ventilation. Did the authors find that endothelial function and atherosclerosis were useful in predicting major clinical outcomes of COVID-19 patients? This study lends further insight into understanding the role of reduced flow mediated dilation in mediating the negative effects of COVID on cardiovascular health. Listen to find out why.
Michelle Cristina-Oliveira, Kamila Meireles, Saulo Gil, Fábio Cavalcante Assis, João Carlos Geber-Júnior, Samuel Katsuyuki Shinjo, Heraldo Possolo de Souza, Alfredo Nicodemos Cruz Santana, Paul A. Swinton, Luciano F. Drager, Bruno Gualano, Hamilton Roschel, and Tiago Peçanha Carotid intima-media thickness and flow-mediated dilation do not predict acute in-hospital outcomes in patients hospitalized with COVID-19 Am J Physiol Heart Circ Physiol, published April 22, 2022. DOI: 10.1152/ajpheart.00026.2022
How does in utero glucocorticoid administration impact autonomic control of the heart in adult offspring in a sex-dependent manner? In this episode, Associate Editor Dr. Crystal Ripplinger (University of California – Davis) interviews authors Dr. Taben Hale and Lakshmi Madhavpeddi (University of Arizona) along with expert Dr. Glen Pyle (University of Guelph) about the new work by Madhavpeddi et al. The authors administered dexamethasone to pregnant rats using a dose and timing that closely mimicked clinical application of dexamethasone administration to pregnant women at risk for preterm delivery to prevent respiratory distress in newborns. At baseline, the authors did not observe any differences between the prenatally-exposed offspring and controls. In response to an experimental stressor, however, the authors found that prenatal exposure to dexamethasone resulted in exaggerated blood pressure and heart rate only in adult female rats. Prenatally-exposed adult male rats did not exhibit any stress response changes in cardiovascular function. In addition, only the dexamethasone-exposed adult female offspring showed a reduction in the high frequency component of heart rate variability, indicating withdrawal of parasympathetic activity. What role does angiotensin II play in the altered autonomic response induced by prenatal dexamethasone exposure? Can we derive important potential clinical applications of this work related to the long-term impact on offspring from treatments administered during their mothers’ pregnancies? Listen now to find out.
L. Madhavpeddi, B. Hammond, D. L. Carbone, P. Kang, R. J Handa, T. M. Hale Impact of angiotensin II receptor antagonism on the sex-selective dysregulation of cardiovascular function induced by in utero dexamethasone exposure Am J Physiol Heart Circ Physiol, published March 17, 2022. DOI: 10.1152/ajpheart.00587.2021
Who knew that back in 2010, when previous Editor-in-Chief Dr. Bill Stanley said, “Podcasts! I don’t know anything about them, but I think we should do them!,” that we would still be producing The AJP-Heart and Circ Podcast 12 years and 299 episodes later?! Since then we have talked with hundreds of authors, experts and editors around the world about the innovative and impactful research published in AJP-Heart and Circulatory Physiology. In this special anniversary episode #300, we turn the tables on our usual format. Executive Editor and podcast producer Kara Hansell Keehan interviews Editor-in-Chief Dr. Merry Lindsey (University of Nebraska Medical Center), Deputy Editor Dr. Zamaneh Kassiri (University of Alberta), and Associate Editors Dr. Keith Brunt (Dalhousie University), Dr. Jason Carter (Montana State University), Dr. Jonathan Kirk (Loyola University Chicago), Dr. Petra Kleinbongard (University of Duisburg-Essen Medical School), Dr. Amanda Jo LeBlanc (University of Louisville), and Dr. Crystal Ripplinger (University of California-Davis). Why should authors submit to AJP-Heart and Circ? What advice do the AJP-Heart and Circ editors have for early career researchers? And finally, what do the editors have to say about the value of The AJP-Heart and Circ Podcast for our listeners? There is only one way to find out. Listen now.
Are failing hearts addicted to glutamine? In this special episode of The AJP-Heart and Circ Podcast, we bring you a conversation in both Japanese and English with Editorial Board member Dr. Junichi Sadoshima (Rutgers University-New Jersey Medical School), Consulting Editor Dr. Jun Yoshioka (City University of New York School of Medicine), and corresponding author Dr. Manabu Nagao (Kobe University Graduate School of Medicine) about the new study by Yoshikawa et al. that explores the interaction between metabolism and pathophysiological cardiac hypertrophy. It is well known that the heart uses various substrates to produce ATP during cardiac hypertrophy. Earlier observations about how cancer cells rapidly consume glutamine during the tumor growth phase led the authors to interrogate the role of glutamine metabolism in cardiac hypertrophy. Nagao and co-authors show that glutaminase is upregulated during cardiac hypertrophy, and that suppression of glutaminase 1 (GLS1) attenuates cardiac hypertrophy. GLS1-mediated glutaminolysis contributes to maladaptive cardiac remodeling by increasing anabolic reactions for hypertrophy and proliferation. Glutamine metabolism is essential for cardiomyocytes. Interestingly, glutaminolysis is activated much faster than glucolysis in response to acute stress. Yoshikawa et al. show that a counter-clockwise shift of the tricarboxylic acid cycle contributes to cardiac remodeling. This study is a game-changer. Listen to learn why.
Sachiko Yoshikawa, Manabu Nagao, Ryuji Toh, Masakazu Shinohara, Takuya Iino, Yasuhiro Irino, Makoto Nishimori, Hidekazu Tanaka, Seimi Satomi-Kobayashi, Tatsuro Ishida, and Ken-Ichi Hirata Inhibition of glutaminase 1-mediated glutaminolysis improves pathological cardiac remodeling Am J Physiol Heart Circ Physiol, published March 30, 2022. DOI: 10.1152/ajpheart.00692.2021
Are failing hearts addicted to glutamine? In this special episode of The AJP-Heart and Circ Podcast, we bring you a conversation in both Japanese and English with Editorial Board member Dr. Junichi Sadoshima (Rutgers University-New Jersey Medical School), Consulting Editor Dr. Jun Yoshioka (City University of New York School of Medicine), and corresponding author Dr. Manabu Nagao (Kobe University Graduate School of Medicine) about the new study by Yoshikawa et al. that explores the interaction between metabolism and pathophysiological cardiac hypertrophy. It is well known that the heart uses various substrates to produce ATP during cardiac hypertrophy. Earlier observations about how cancer cells rapidly consume glutamine during the tumor growth phase led the authors to interrogate the role of glutamine metabolism in cardiac hypertrophy. Nagao and co-authors show that glutaminase is upregulated during cardiac hypertrophy, and that suppression of glutaminase 1 (GLS1) attenuates cardiac hypertrophy. GLS1-mediated glutaminolysis contributes to maladaptive cardiac remodeling by increasing anabolic reactions for hypertrophy and proliferation. Glutamine metabolism is essential for cardiomyocytes. Interestingly, glutaminolysis is activated much faster than glucolysis in response to acute stress. Yoshikawa et al. show that a counter-clockwise shift of the tricarboxylic acid cycle contributes to cardiac remodeling. This study is a game-changer. Listen to learn why.
Sachiko Yoshikawa, Manabu Nagao, Ryuji Toh, Masakazu Shinohara, Takuya Iino, Yasuhiro Irino, Makoto Nishimori, Hidekazu Tanaka, Seimi Satomi-Kobayashi, Tatsuro Ishida, and Ken-Ichi Hirata Inhibition of glutaminase 1-mediated glutaminolysis improves pathological cardiac remodeling Am J Physiol Heart Circ Physiol, published March 30, 2022. DOI: 10.1152/ajpheart.00692.2021
Impactful findings with reverberating consequences – this is what AJP-Heart and Circ Rapid Reports are here for. Listen as Associate Editor Dr. Jonathan Kirk (Loyola University Chicago Stritch School of Medicine) interviews lead author Dr. Susan Steinberg (Columbia University) and expert Dr. Michael Kapiloff (Stanford University) about this novel work by Zhu and Steinberg. More than 20 years ago, Steinberg and collaborators used immunoblot analysis to implicate compartmentalization as a mechanism that imparts beta-adrenergic receptor subtype signaling specificity. Of note, these studies also provided the unexpected observation that the beta1-adrenergic receptor subtype accumulates as both full-length and N-terminally truncated species; in contrast, beta2-adrenergic receptors are expressed exclusively as a single full-length species. The Steinberg laboratory went on to identify the molecular mechanisms that control the maturational processing of the full-length receptor to an N-terminally truncated form (including the role of a member of the matrix metalloproteinase family of enzymes) and the functional importance of this finding. They showed that full-length and N-terminally truncated beta1-adenergic receptors differ in their signaling phenotype; the N-terminally truncated beta1-adenergic receptor plays a unique role to constitutively activate an AKT signaling pathway that is cardioprotective.
This Rapid Report expands upon the previous studies by showing that the beta1-adrenergic receptor is also cleaved by trypsin, an enzyme used in protocols to isolate cardiomyocytes from ventricular tissue. This finding suggests that studies on cardiomyocytes isolated in this manner should be interpreted with caution. In the broader context, the cleavage mechanism that regulates beta1-adrenergic receptor signaling uncovered by Zhu and Steinberg has important clinical implications given the fact that beta-adrenergic receptors are first-line targets for heart failure (with beta blockers one of the most prescribed medications). The podcast discusses several questions. Are beta1-adrenergic receptors also cleaved (and hence catecholamine responsiveness also altered) by functionally relevant inflammatory proteases in the setting of cardiac injury or myocarditis? Do the full-length and truncated forms of the beta1-adrenergic receptor play distinct roles in the evolution of heart failure? This research clearly is a springboard for future studies. Listen and find out why.
Jing Zhu and Susan F. Steinberg Trypsin cleavage of the beta1-adrenergic receptor Am J Physiol Heart Circ Physiol, published March 1, 2022. DOI: 10.1152/ajpheart.00005.2022
While echocardiography is commonly used to assess cardiac structure and function in mouse models of heart disease, can this non-invasive technique also be used to accurately measure infarct size? Listen as Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) interviews co-authors Dr. Erin Mulvihill (University of Ottawa) and Dr. Craig Goergen (Purdue University), along with content expert Dr. Daniele Panetta (Institute of Clinical Physiology CNR - Pisa). Dann et al. measured and monitored infarct size by comparing and contrasting 2-D echo imaging results with 4-D echo imaging results in a myocardial infarction mouse model. 4-D ultrasound imaging allowed the authors to measure the entire volume of the left ventricle throughout the cardiac cycle, as well as analyze the progression of asymmetric ventricular remodeling. In addition, this work illustrates how authors from two different academic institutions found a novel way to collaborate during the COVID-19 pandemic and ensuing international travel restrictions. The study by Dann et al. provides a unique visualization of the infarct in 3-D, which then allowed for volumetric analysis to use contouring of the heart to produce dynamic strain maps. Listen as we discuss how the innovative imaging modalities utilized by Dann et al. allow researchers to focus on animal specific differences as well as the inclusion of both female and male animals for robust rigor and reproducibility.
Melissa M. Dann, Sydney Q. Clark, Natasha A. Trzaskalski, Conner C. Earl, Luke E. Schepers, Serena M. Pulente, Ebonee N. Lennord, Karthik Annamalai, Joseph M. Gruber, Abigail D. Cox, Ilka Lorenzen-Schmidt, Richard Seymour, Kyoung-Han Kim, Craig J. Goergen, and Erin E. Mulvihill Quantification of murine myocardial infarct size using 2-D and 4-D high-frequency ultrasound
Am J Physiol Heart Circ Physiol, published February 8, 2022. DOI: doi.org/10.1152/ajpheart.00476.2021
Despite the establishment of NIH guidelines for inclusion of women in clinical studies, as well as clear expectations for rigor and reproducibility in reporting sex as a biological variable in NIH grant submissions, women and females are still understudied populations in human and animal research. Enter this important primer on incorporating sex as a biological variable into basic and clinical research. Listen as Consulting Editor Austin Robinson, PhD (Assistant Professor, Neurovascular Physiology Laboratory, Auburn University) interviews lead author Quin Denfeld, PhD, RN (Assistant Professor, School of Nursing and Division of Cardiovascular Medicine, School of Medicine, Oregon Health & Science University) and women’s health expert Judith Regensteiner, PhD (Director of the Ludeman Family Center for Women’s Health Research and Professor of Medicine, Divisions of Internal Medicine and Cardiology, University of Colorado Anschutz Medical Campus). Denfeld and co-authors heeded the call to action outlined in the recent editorial by the AJP-Heart and Circ Editors on “Reinforcing rigor and reproducibility expectations for use of sex and gender in cardiovascular research”, along with its accompanying podcast episode and Call for Papers on Considering Sex as a Biological Variable in Cardiovascular Research.
In their Perspective article, Denfeld et al. offered practical and actionable ideas for how to include women and females in research studies, demystifying the process for fellow researchers by addressing common concerns such as sample size, cost, statistical analysis, and study participant recruitment challenges. In this episode, our experts tackled these subjects head on, championing the value of looking at data, even pilot data, through the lens of sex differences.
Don’t miss hearing about career development opportunities available to researchers from the NIH Office of Research on Women’s Health and Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program. Including both sexes and genders in research studies is not difficult to accomplish with foresight, planning, and perhaps a little creative thinking. This insightful conversation is invaluable to all researchers. Listen now.
Recommended Reading in AJP-Heart and Circ:
Quin E. Denfeld, Christopher S. Lee, and Beth A. Habecker A primer on incorporating sex as a biological variable into the conduct and reporting of basic and clinical research studies Am J Physiol Heart Circ Physiol, published February 8, 2022. DOI: 10.1152/ajpheart.00605.2021
Austin T. Robinson, Megan M. Wenner, Kanokwan Bunsawat, Joseph C. Watso, Gabrielle E. W. Giersch, and Nisha Charkoudian When it’s time for the sex talk, words matter Am J Physiol Heart Circ Physiol, published December 13, 2021. DOI: 10.1152/ajpheart.00556.2021
Special Article Collection on Considering Sex as a Biological Variable
Deciding on the best mouse model to research myocardial ischemic injury? Stop and listen. Associate Editor Jason Carter (Montana State University) interviewed authors Zamaneh Kassiri (University of Alberta), Crystal Ripplinger (University of California Davis), John Calvert (Emory University), Kristine DeLeon-Pennell (University of South Carolina), Dominic Del Re (Rutgers New Jersey Medical School), Richard Gumina (The Ohio State University), Steven Jones (University of Louisville), and Ganesh Halade (University of South Florida). Representing the distinguished group of experts who collaborated on “Guidelines for in vivo mouse models of myocardial infarction” by Lindsey et al., these authors discussed their consensus article that documents strategies for inducing and evaluating reperfused and non-reperfused myocardial infarction mouse models. The authors emphasized that one model is not superior to another model, but rather each model addresses a different set of scientific questions. The authors also discussed comprehensive experimental design, inclusion of both male and female mice, sample sizes for sufficient statistical power analyses, and statistical tests mapped to the number of variables studied. In addition, the authors touched on providing benchmarks for left ventricular remodeling and function resulting from MI, reporting anesthetics and analgesics used in studies, and measurements and reporting of infarct size using standardized methods. This is a unique opportunity to hear how the authors navigated differing points of view to create an insightful roadmap for the field. The comprehensive checklist in Table 4 is particularly useful for new investigators. Early career researchers – add this to your playlist!
Merry L. Lindsey, Keith R. Brunt, Jonathan A. Kirk, Petra Kleinbongard, John W. Calvert, Lisandra E. de Castro Brás, Kristine Y. DeLeon-Pennell, Dominic P. Del Re, Nikolaos G. Frangogiannis, Stefan Frantz, Richard J. Gumina, Ganesh V. Halade, Steven P. Jones, Rebecca H. Ritchie, Francis G. Spinale, Edward B. Thorp, Crystal M. Ripplinger, Zamaneh Kassiri Guidelines for in vivo mouse models of myocardial infarction Am J Physiol Heart Circ Physiol, published November 17, 2021. DOI: doi.org/10.1152/ajpheart.00459.2021
Listeners, we are bringing you a special cross-over event with The AJP-Heart and Circ Podcast. In our January 2022 episode on Cortical Bone Stem Cells Effects on Cardiac Wound Healing, we talked with senior authors Dr. Steven Houser and Dr. Timothy McKinsey about their collaboration on two recently published articles by Hobby et al. and Schena et al. In this new episode of Behind the Bench, hosts Dr. Lisandra de Castro Brás (East Carolina University) and Dr. Charlotte Usselman (McGill University) interview first authors Dr. Alexander Hobby (University of Colorado Anschutz Medical Campus) and Dr. Giana Schena (Rajant Corporation). Why two podcast episodes on the same two articles? The studies represent a unique collaboration between the Houser Lab and the McKinsey Lab, and Alex and Giana are both former Houser Lab members who have pursued different paths. Alex transitioned to a post-doc position in the McKinsey Lab doing molecular studies, a departure from the large animal studies he conducted in the Houser Lab. Giana moved from academia to industry, working for Rajant Health, a healthcare business division of Rajant Corporation. Both Alex and Giana have unique perspectives that will resonate with anyone determining which path to take next in their science career. Give a listen.
Giana J. Schena, Emma K. Murray, Alycia N. Hildebrand, Alaina L. Headrick, Yijun Yang, Keith A. Koch, Hajime Kubo, Deborah Eaton, Jaslyn Johnson, Remus Berretta, Sadia Mohsin, Raj Kishore, Timothy A. McKinsey, John W. Elrod, and Steven R. Houser Cortical bone stem cell-derived exosomes’ therapeutic effect on myocardial ischemia-reperfusion and cardiac remodeling Am J Physiol Heart Circ Physiol, published November 8, 2021. DOI: 10.1152/ajpheart.00197.2021
Alexander R. H. Hobby, Remus M. Berretta, Deborah M. Eaton, Hajime Kubo, Eric Feldsott, Yijun Yang, Alaina L. Headrick, Keith A. Koch, Marcello Rubino, Justin Kurian, Mohsin Khan, Yinfei Tan, Sadia Mohsin, Stefania Gallucci, Timothy A. McKinsey, and Steven R. Houser Cortical bone stem cells modify cardiac inflammation after myocardial infarction by inducing a novel macrophage phenotype Am J Physiol Heart Circ Physiol, published September 23, 2021. DOI: 10.1152/ajpheart.00304.2021
In this episode, Associate Editor Amanda LeBlanc (University of Louisville) interviews authors Lacy Alexander and Gabrielle Dillon (The Pennsylvania State University) along with content expert Melissa Witman (University of Delaware) about a new study by Dillon et al. With their lab closed due to the pandemic, the Alexander Lab continued to hold journal club meetings virtually to discuss two articles published previously in AJP-Heart and Circ – Ratchford et al. and Nandadeva et al. The intriguing results in these studies became a catalyst for new research questions which the Alexander Lab began to pursue as soon as they could return to human research post-pandemic. In contrast to both Ratchford et al. and Nandadeva et al., Dillon et al. found that healthy young adults who had recovered from mild to moderate COVID-19 did not display alterations in nitric oxide-mediated cutaneous microvascular function. The authors hypothesized that methodology, onset of symptomology, and the role of vaccine-generated antibodies are key reasons their results differed from other recent studies. In addition, the authors found that having vaccine-generated antibodies was not detrimental to the microvasculature. The authors navigated numerous roadblocks in undertaking this study—stringent COVID-19 health and safety measures, scarce PPE, difficulty enrolling participants, and required COVID-19 testing protocols prior to participation. When faced with the decision on how to handle enrolling fully vaccinated, partially vaccinated and unvaccinated subjects, the authors opted to include all and stratify their results. This is an episode as much about resilience as it is about research. In search of inspiration for how to pivot and keep moving forward? Listen now.
Gabrielle A. Dillon, S. Tony Wolf, and Lacy M. Alexander Nitric oxide-mediated cutaneous microvascular function is not altered in young adults following mild-to-moderate SARS CoV-2 infection Am J Physiol Heart Circ Physiol, published January 28, 2022. DOI: doi.org/10.1152/ajpheart.00602.2021
What’s better than discussing one paper on the effects of cortical bone stem cells and their impact on myocardial infarction? Discussing two papers! Associate Editor Dr. Jonathan Kirk (Loyola University Chicago Stritch School of Medicine) interviews lead authors Dr. Timothy McKinsey (University of Colorado Anschutz Medical Campus) and Dr. Steven R. Houser (Lewis Katz School of Medicine at Temple University) along with expert Dr. Helen Collins (University of Louisville School of Medicine). The latest collaborations from the Houser lab and the McKinsey lab could pave the way for significant advancements in understanding how exosomes derived from cortical bone stem cells (CBSCs) may have the ability to reduce injury from acute myocardial infarction (MI). In the study by Schena et al., Houser and co-authors used an ischemia/reperfusion model and found that, if given soon enough after injury, CBSC-derived exosomes had an acute protective effect on infarct size. The authors then found that secreted factors from CBSCs and their exosomes modified fibroblasts in ways that likely alter MI scar formation. In the study by Hobby et al., McKinsey and co-authors found that CBSCs influence macrophage polarity in vitro toward an anti-inflammatory protective phenotype. Those macrophages, which had been treated with CBSC-derived factors, influenced fibroblasts to become less fibrotic yet more proliferative. Enter small nucleolar RNA (snoRNA) into this story as important regulators of protein translation. Downregulating snoRNAs in turn downregulated protein translation and blocked fibroblast activation. Our experts discuss the advantages and challenges of conducting large animal studies, the opportunities for discovery with snoRNAs, and the exciting future ahead for translational heart failure research. Listen and learn more.
Giana J. Schena, Emma K. Murray, Alycia N. Hildebrand, Alaina L. Headrick, Yijun Yang, Keith A. Koch, Hajime Kubo, Deborah Eaton, Jaslyn Johnson, Remus Berretta, Sadia Mohsin, Raj Kishore, Timothy A. McKinsey, John W. Elrod, and Steven R. Houser Cortical bone stem cell-derived exosomes’ therapeutic effect on myocardial ischemia-reperfusion and cardiac remodeling Am J Physiol Heart Circ Physiol, published November 8, 2021. DOI: 10.1152/ajpheart.00197.2021
Alexander R. H. Hobby, Remus M. Berretta, Deborah M. Eaton, Hajime Kubo, Eric Feldsott, Yijun Yang, Alaina L. Headrick, Keith A. Koch, Marcello Rubino, Justin Kurian, Mohsin Khan, Yinfei Tan, Sadia Mohsin, Stefania Gallucci, Timothy A. McKinsey, and Steven R. Houser Cortical bone stem cells modify cardiac inflammation after myocardial infarction by inducing a novel macrophage phenotype Am J Physiol Heart Circ Physiol, published September 23, 2021. DOI: 10.1152/ajpheart.00304.2021
Permeability is an important measure of the exchange function of microvessels, but until now, there has been a lack of physiologically-relevant in vitro microvessel models that allow an easy assessment of permeability properties of the microvessel wall. In our latest episode, Associate Editor Amanda LeBlanc (University of Louisville) interviews lead author Ping He (Penn State University) and expert Robert Hester (University of Mississippi Medical Center) about the latest research study by Gao et al., published in the AJP-Heart and Circ Call for Papers on Deconstructing Organs: Single-Cell Analyses, Decellularized Organs, Organoids, and Organ-on-a-Chip Models. Dr. He and colleagues developed a novel microvessel-on-a-chip model which allows endothelial cells to grow under continuous flow, simulating the in vivo environment, while also allowing for the assessment barrier function of the microvessel wall. The in vitro microvessel model Gao et al. developed features layers of glycocalyx and endothelium, and as Dr. He points out, endothelial junctions and glycocalyx are key components contributing to microvessel barrier function and acute inflammatory responses observed in in vivo models. Listen as we discuss the future directions of this model in both acute and chronic conditions, disease states and future molecular studies.
Feng Gao, Haoyu Sun, Xiang Li, Pingnian He Leveraging avidin/biotin interaction to quantify permeability of microvessels-on-a-chip Am J Physiol Heart Circ Physiol, published December 13, 2021. DOI: 10.1152/ajpheart.00478.2021
It is well known that exercise can have beneficial effects on brain health, including reducing the risk of dementia and stroke. Does resistance exercise training affect brain blood flow and cerebrovascular physiology differently than endurance exercise? Guest Host Brady Holmer (University of Florida) interviews first author Hannah Thomas (The University of Western Australia) and expert Timo Klein (University of Rostock) about the latest research by Thomas and co-authors which directly compared adaptations in the brain and cerebrovascular function to these two different exercise modalities. Using a randomized cross-over study design to directly compare participant responses to resistance exercise and endurance exercise, young healthy individuals completed 3 months of resistance training 3 times per week, followed by 3 months of endurance training 3 times per week. To develop a comprehensive picture of adaptations occurring in the cerebrovasculature of the study participants, Thomas and collaborators measured middle and posterior cerebral arteries using transcranial Doppler ultrasound to determine blood velocity. In addition, Thomas et al. measured internal carotid and vertebral arteries using duplex ultrasound to assess both diameter and blood flow velocity. What changes in cerebrovascular function did Thomas et al. find in response to resistance training that were not found in response to endurance training? Could these findings lead to possible clinical applications of exercise as preventative therapy for aging, cognitive impairment, and cerebrovascular dysfunction related to dementia? Listen now.
Hannah J. Thomas, Channa E. Marsh, Louise H. Naylor, Philip N. Ainslie, Kurt J. Smith, Howard H. Carter, and Daniel J. Green Resistance, but not endurance exercise training, induces changes in cerebrovascular function in healthy young subjects Am J Physiol Heart Circ Physiol, published October 11, 2021. DOI: 10.1152/ajpheart.00230.2021
What are the goals and expectations of AJP-Heart and Circulatory Physiology over the next several years to optimize rigorous approaches to consideration of sex and gender as a biological variable in cardiovascular research? Consulting Editor Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine) interviews the entire AJP-Heart and Circ editorial team in this pivotal episode of The AJP-Heart and Circ Podcast. Listen as Editor-in-Chief Merry Lindsey (University of Nebraska Medical Center), Deputy Editor Zamaneh Kassiri (University of Alberta), and Associate Editors Keith Brunt (Dalhousie University), Jason Carter (Montana State University), Jonathan Kirk (Loyola University Chicago), Petra Kleinbongard (University of Duisburg-Essen Medical School), Amanda Jo LeBlanc (University of Louisville), Crystal Ripplinger (University of California-Davis) and Executive Editor Kara Hansell Keehan (American Physiological Society) discuss their recent editorial on expectations for use of sex and gender in cardiovascular research published in AJP-Heart and Circ. The editorial team first assessed reporting of sex and gender in AJP-Heart and Circ articles, and found that, while most studies did report sex/gender, most studies did not use both sexes/genders. By January 2023, AJP-Heart and Circ expects authors to use both sexes/genders in studies submitted to the journal, unless there is strong scientific justification otherwise. What constitutes “strong scientific justification”? Do studies need to be sufficiently powered to detect sex differences? How should authors analyze aggregate data? We tackle these questions in the context of human physiology, small and large animal models, and cell physiology. Why use both sexes/genders? “Put simply, it’s only going to make the research stronger,” stated Jason Carter. This is a must-listen episode!
Merry L. Lindsey, Amanda J. LeBlanc, Crystal M. Ripplinger, Jason R. Carter, Jonathan A. Kirk, Kara Hansell Keehan, Keith R. Brunt, Petra Kleinbongard, and Zamaneh Kassiri Reinforcing rigor and reproducibility expectations for use of sex and gender in cardiovascular research Am J Physiol Heart Circ Physiol, published September 15, 2021. DOI: 10.1152/ajpheart.00418.2021
What is the causal relationship between high-level spinal cord injury, orthostatic hypotension and increased risk for cardiovascular disease? In this episode, Consulting Editor Patrick Osei-Owusu (Case Western Reserve University) interviews authors Christopher West (University of British Columbia) and Aaron Phillips (University of Calgary), along with expert Jill Wecht (James J. Peters VA Medical Center) about the new study by Hayes et al. High-level spinal cord injury can lead to orthostatic hypotension, a debilitating condition experienced by a substantial number of both cervical and high thoracic spinal cord injury (SCI) patients. Yet how this impacts the heart and cerebral vasculature is not well understood in this population. By creating a novel experimental animal model of lower body negative pressure, the authors were able to study how the brain vasculature and heart respond to an orthostatic challenge. Hayes et al. first quantified how much negative pressure was needed to replicate clinically-relevant orthostatic hypotension in rodents with SCI. The authors then introduced the lower body negative pressure technique, and measured cardiac pressure and volume responses in rodents with and without SCI. Finally, the authors imaged the mid-cerebral artery and analyzed step-wise reductions in blood pressure during lower body negative pressure to understand the relationship of pressure to flow in the cerebrovasculature in rodents with and without SCI. What did the authors find and what is the clinical significance of this novel experimental model of lower body negative pressure that allows for real-time micro-analysis in multiple organ systems? Listen to find out.
Brian D. Hayes, Mary Pauline Mona Fossey, Malihe-Sadat Poormasjedi-Meibod, Erin Erskine, Jan Elaine Soriano, Berkeley Scott, Ryan Rosentreter, David J. Granville, Aaron A. Phillips, and Christopher R. West Experimental high thoracic spinal cord injury impairs the cardiac and cerebrovascular response to orthostatic challenge in rats Am J Physiol Heart Circ Physiol, published September 23, 2021. DOI: 10.1152/ajpheart.00239.2021
How do β-adrenergic receptor subtypes regulate immune function in the heart? In this unique episode of The AJP-Heart and Circ Podcast, Consulting Editor Dr. Kristine DeLeon-Pennell (Medical University of South Carolina) interviews two authors about their two articles published recently in AJP-Heart and Circulatory Physiology. Dr. Laurel Grisanti (University of Missouri, Columbia) discussed her study (Tanner et al.) on the important role for β2-adrenergic receptor expression on immune cells in the development of heart failure in response to chronic catecholamine elevation. Using a chronic isoproterenol infusion model of heart failure, Dr. Grisanti and co-authors concluded that the immune cell expression of β2-adrenergic receptor is an important contributor to the detrimental responses seen with chronic elevations in catecholamine. The macrophage populations lacking β2-adrenergic receptor largely retained their reparative phenotype and failed to illicit pro-inflammatory macrophage recruitment. Dr. Petra Eder-Negrin (University Hospital, Würzburg) discussed her work (Cellini et al.) in context of Dr. Grisanti's study, underscoring the mechanistic link between sodium potassium -ATPase and β-adrenergic stimulation in the post-MI heart. Eder-Negrin and co-authors found that sodium potassium ATPase alpha 2 overexpressing cardiomyocytes are a crucial adaption, providing an important functional reserve for the heart to cope with chronic stress more efficiently. Sodium potassium ATPase alpha 2 overexpression could be an alteration to attenuate heart failure. How do these research studies connect? Listen now.
Miles A. Tanner, Charles A. Maitz, and Laurel A. Grisanti Immune cell β2-adrenergic receptors contribute to the development of heart failure Am J Physiol Heart Circ Physiol, published September 15, 2021. DOI: 10.1152/ajpheart.00243.2021
Antonella Cellini, Dorina Höfler, Paula A. Arias-Loza, Sandra Bandleon, Tanja Langsenlehner, Michael Kohlhaas, Christoph Maack, Wolfgang R. Bauer, and Petra Eder-Negrin The α2-isoform of the Na+/K+-ATPase protects against pathological remodeling and β-adrenergic desensitization after myocardial infarction Am J Physiol Heart Circ Physiol, published September 15, 2021. DOI: 10.1152/ajpheart.00808.2020
Is the loss of endothelin-B receptor mediated vasodilation in women after menopause due to aging or the decline in estradiol that occurs with menopause? Associate Editor Dr. Jason Carter (Montana State University) interviews senior author Megan Wenner (University of Delaware) and content expert Lacy Alexander (Pennsylvania State University) about the work by Wenner and co-authors to isolate and study specific effects of estradiol on the regulation of the ETB receptor. Shoemaker et al. enrolled young women in their study and utilized an endogenous hormone suppression with estradiol add-back experimental design to eliminate changes related to aging and other sex hormones. Wenner and collaborators then measured microvascular endothelial function using laser Doppler flowmetry while perfusing an antagonist for the ETB receptor via intradermal microdialysis fiber, a technique pioneered by Lacy Alexander. The authors found that when estradiol is present, the ETB receptor mediates vasodilation. However, when estradiol is absent or suppressed, ETB-mediated dilation is lost. Bottom line: changes in estradiol regulate the function of this ETB receptor. What is the clinical relevance of this work for women’s health, in particular related to endometriosis, premature ovarian failure, and other pathophysiological conditions related to dysregulated sex hormones? Listen to learn more about this fascinating study and its implications on women’s overall cardiovascular health.
Leena N. Shoemaker, Katherine M. Haigh, Andrew V. Kuczmarski, Shane J. McGinty, Laura M. Welti, Joshua C. Hobson, David G. Edwards, Ronald F. Feinberg, and Megan M. Wenner ETB receptor-mediated vasodilation is regulated by estradiol in young women
Am J Physiol Heart Circ Physiol, published September 3, 2021.
DOI: 10.1152/ajpheart.00087.2021
Is cardiac remodeling associated with an increase in left ventricular dyssynchrony and post-systolic shortening in young bodybuilders using anabolic-androgenic steroids? Guest Host Brady Holmer (University of Florida) interviews lead author Stéphane Nottin (Avignon University) and content expert Austin Robinson (Auburn University) to get the answers. The groundbreaking work by Grandperrin et al. is the first study to investigate the presence of LV dyssynchrony in strength-trained male athletes using anabolic-androgenic steroids. Black-market steroids are illegal in most sports, yet easily available to athletes on the internet. It is well documented in the literature that use of anabolic-androgenic steroids by strength-trained athletes leads to deleterious cardiac hypertrophy with non-reversible myocardial dysfunction. The authors studied three groups: 1) young male bodybuilders who self-reported substantial use of anabolic-androgenic steroids; 2) young male bodybuilders who self-reported to have never used anabolic-androgenic steroids; 3) young untrained control subjects. Nottin and co-authors evaluated regional strains via resting echocardiography, and found that the group of young male bodybuilders who reported substantial steroid use showed increased LV mechanical dispersion, which correlated with increased LV mass and LV post-systolic shortening. Our experts discuss long term cardiovascular risks to anabolic-androgenic steroid users, as well as future directions and unique techniques needed to study female bodybuilders using anabolic-androgenic steroids. This episode is a must-listen for athletes, coaches, and exercise physiologists alike. Listen now.
Antoine Grandperrin, Iris Schuster, Thomas Rupp, Omar Izem, Philippe Obert, and Stéphane Nottin Left ventricular dyssynchrony and post-systolic shortening in young bodybuilders using anabolic-androgenic steroids Am J Physiol Heart Circ Physiol, published August 25, 2021. DOI: 10.1152/ajpheart.00136.2021
Allow us to introduce you to Tommy Martin, a trainee in The Kirk Lab at Loyola University Chicago, who is scheduled to defend his PhD thesis in October 2021. Tommy is first author on a recently published AJP-Heart and Circ article, which is co-authored by Jonathan Kirk, an Associate Editor for AJP-Heart and Circ, and a founding member of our Behind the Bench podcast crew. Tommy has a story that will resonate with trainees and early career researchers: he was vacillating between going to medical school and getting a PhD. His interview with the very personable and enthusiastic Jonathan Kirk was the deciding factor to take the fork in the road that led to graduate school for a PhD in cardiovascular research. Our intrepid Behind the Bench co-hosts Lisandra de Castro Brás (East Carolina University) and Charlotte Usselman (McGill University) interview Tommy about life in the lab as a would-be medical student, learning how to use a pipette for the first time, his best advice to trainees for how to nail the post-doc interview process, and the drive and commitment necessary to pursue success in science. We also get the inside scoop about all things Jonathan Kirk (that beard!), and along the way we manage to discuss BAG3 protein expression in sarcomeric proteins in heart failure. Tommy Martin is engaging, sharp and clearly a rising star in cardiovascular research. Listen now, and don’t miss the bonus outtake after the credits.
Thomas G. Martin, Sara Tawfik, Christine S. Moravec, Toni R. Pak, Jonathan A. Kirk BAG3 expression and sarcomere localization in the human heart are linked to HSF-1 and are differentially affected by sex and disease Am J Physiol Heart Circ Physiol, published May 26, 2021. DOI: 10.1152/ajpheart.00419.2020
How does a single intriguing patient encounter lead to a clinical research career investigating extreme premature birth history and increased risk of cardiopulmonary complications later in life? In this new episode of Behind the Bench with AJP-Heart and Circ, co-hosts Lisandra de Castro Brás (East Carolina University) and Charlotte Usselman (McGill University) interview Kara Goss (University of Texas Southwestern) about the fascinating study by Corrado et al. Admittedly inspired by her own experience as a mother to two children, both of whom were born prematurely, our producer Kara Hansell Keehan wanted to dig deeper into this latest work by Goss and co-authors. An early inspiration for Goss was her clinical rotation in the NICU, yet she followed a different clinical path into adult critical cardiopulmonary care. It was ultimately a single encounter with an older patient in acute cardiopulmonary distress who had, as Goss uncovered, a preterm birth history, that changed her career path. Thus, a research career was born (pun intended). Why did Goss and co-authors find right ventricular, but not left ventricular, dysfunction in this former preemie adult cohort? Is exercise the key to mitigating the effects of this right ventricular function? This podcast episode is simply fascinating, so listen now.
Philip A. Corrado, Gregory P. Barton, Christopher J. Francois, Oliver Wieben, and Kara N. Goss Sildenafil administration improves right ventricular function on 4D flow MRI in young adults born premature Am J Physiol Heart Circ Physiol, published May 20, 2021. DOI: doi.org/ 10.1152/ajpheart.00824.2020
This is a story about a good guy (thioredoxin) vs. a bad guy (Txnip). Consulting Editor Paras Mishra (University of Nebraska Medical Center) interviews lead author Jun Yoshioka (City University of New York) and expert Rebecca Ritchie (Monash University) about the latest research by Yoshioka and co-authors. As the underlying basis of diabetic cardiomyopathy remains unclear, Mukai et al. focused on the pathway connecting hyperglycemia to oxidative stress. Thioredoxin is an antioxidant molecule which uses catalytic sites at cysteine 32 and 35 to reduce target proteins and detoxify oxidative stress. The villain Txnip, an endogenous inhibitor of thioredoxin and its antioxidative properties, acts as a pro-oxidant. A high level of extracellular glucose strongly upregulates Txnip. “If glucose induces Txnip, and Txnip is a bad guy killing cells, then the obvious question is: does Txnip mediate diabetes-induced cellular damage?” explains Yoshioka. What’s the answer? Listen now.
Nobuhiro Mukai, Yoshinobu Nakayama, Syed Amir Abdali, Jun Yoshioka Cardiomyocyte-specific Txnip C247S mutation improves left ventricular functional reserve in streptozotocin-induced diabetic mice Am J Physiol Heart Circ Physiol, published June 4, 2021. DOI: 10.1152/ajpheart.00174.2021
Does maternal vaping cause brain blood vessels to behave abnormally in offspring? The short answer: yes. Consulting Editor Junie Paula Warrington (University of Mississippi Medical Center) interviews authors Mark Olfert and Paul Chantler (both at West Virginia University School of Medicine), along with expert Alex Carll (University of Louisville) about the latest groundbreaking study by Burrage et al. The authors set out to understand whether exposing pregnant female rats to a low daily dose of e-cigarette aerosol—with or without nicotine—would result in middle cerebral artery dysfunction in the offspring. In this unique study design, the offspring themselves were never directly exposed to e-cigarettes. Olfert, Chantler and co-authors then assessed vascular function in arteries from the brain in pups at multiple postnatal time-points, and found the offspring had significant reduction in the ability of the middle cerebral artery to relax (or vasodilate) when they needed to. The same levels of dysfunction were found in offspring whose mothers were exposed to vaping with nicotine added to the base e-liquid, as well as offspring of mothers who were exposed to vaping without nicotine in the base e-liquid. This data suggested that some component of the e-liquid other than nicotine (such as flavors or base solution) accounted for the dysfunction that was created. What’s more, the authors discovered that the cerebrovascular dysfunction did not resolve over time. Adult rats, even 7 months after birth, displayed similar levels of impairment as the 1-month-old rat pups. This research has sweeping public health implications for those considering vaping as an alternative to smoking when pregnant. Listen now.
E.N. Burrage, Eiman Aboaziza, Lance Hare, Sarah Reppert, Joshua Moore, William T. Goldsmith, Eric E. Kelley, Amber Mills, Duaa Dakhlallah, Paul D. Chantler, I. Mark Olfert Long Term Cerebrovascular Dysfunction in the Offspring from Maternal Electronic Cigarette Use during Pregnancy Am J Physiol Heart Circ Physiol, published June 25, 2021. DOI: doi.org/10.1152/ajpheart.00206.2021
Why does obesity cause hypertension in some individuals but not others? Consulting Editor Dr. Shawn Bender (University of Missouri) interviews authors Stephanie Watts and Greg Fink (both of Michigan State University), along with expert Andreas Beyer (Medical College of Wisconsin), about a new study by Watts et al. Fink and Watts have had a prolific research collaboration for over 20 years investigating the physiology and pharmacology of hypertension. In recent years they have focused on the genetically hypertensive-prone Dahl salt-sensitive rat, which becomes hypertensive on a high fat diet, and the vascular and perivascular mechanisms contributing to this form of hypertension. Zeroing in on endothelial function, basic hyper-reactivity, and perivascular adipose tissue (PVAT) in aortas of Dahl SS rats fed a high fat diet, the authors found vascular dysfunction was more prevalent in males vs. females. Watts and Fink want you to reconsider PVAT as a critically important part of the vasculature, not simply a secretor of anti-contractile substances. Why? Listen now.
Stephanie W. Watts, Emma S. Darios, G. Andres Contreras, Hannah Garver, Gregory D. Fink Male and Female High Fat Fed Dahl SS rats are largely protected from vascular dysfunctions: PVAT contributions reveal sex differences. Am J Physiol Heart Circ Physiol, published June 14, 2021. DOI: doi.org/10.1152/ajpheart.00131.2021
What is the impact of testosterone and exercise on fitness, body composition and strength in otherwise healthy middle-to-older aged men with mild testosterone deficiency? Associate Editor Jason Carter (Montana State University) interviews first author Lauren Chasland (University of Western Australia) and expert Megan Wenner (University of Delaware) about the new study by Chasland et al. Using a rigorous experimental approach which examined the effects of testosterone and exercise independently and in combination over a 12-week timeframe, Chasland and co-authors found that exercise alone was the primary driver of improved aerobic capacity. When assessing impact on body composition, the authors also saw greater decreases in total fat mass in the exercise-only group compared to the testosterone-only and testosterone + exercise groups. However, testosterone alone did increase leg lean mass, a result the authors think may have possible clinical translation for men unable to exercise due to disease or disability. Why did Chasland and collaborators choose a testosterone cream as their T-treatment modality? Did the exercise protocol—a circuit training routine combining cycling and resistance exercise—have an impact on the results? Listen as our experts unpack yet more evidence pointing to exercise as a potent treatment for sex hormone deficiency in aging adults.
Lauren C. Chasland, Bu B. Yeap, Andrew J. Maiorana, Yi X. Chan, Barbara A. Maslen, Brian R. Cooke, Lawrence Dembo, Louise H. Naylor, Daniel J. Green Testosterone and exercise: Effects on fitness, body composition and strength in middle-to-older aged men with low-normal serum testosterone levels Am J Physiol Heart Circ Physiol, published May 3, 2021. DOI: 10.1152/ajpheart.00010.2021
Does stimulation of the soluble guanylate cyclase pathway in late gestation improve intrauterine growth restriction in a reduced uterine perfusion pressure (RUPP) rat model of placental ischemia? In our latest podcast, Stella Goulopoulou (University of North Texas Health Science Center) interviews authors Barbara Alexander and Laura Coats (University of Mississippi Medical Center), along with expert Chris Banek (University of Arizona), about new research by Coats et al. The authors focused specifically on late gestation (day 20 to birth), which provided unique insights when compared to previous work investigating intrauterine growth restriction (IUGR) from gestation day 14 to gestation day 20. After stimulating the soluble guanylate cyclase (sGC) pathway, the authors found neither birth weight nor asymmetrical growth was improved in male offspring. In addition, the IUGR programmed male offspring, who were exposed to stimulation of the sGC pathway during late gestation, continued to develop hypertension at 4 months of age. Many preclinical studies show the benefits of sGC stimulation to the mother early in gestation and assume long-term benefit to the offspring. This work by Coats et al. is both surprising and clinically relevant to the preeclampsia research field, highlighting the crucial need for intervention late in gestation during critical fetal organ development and follow-up after birth. Where does the field go from here? Listen now.
Laura E. Coats, Bhavisha A. Bakrania, Daniel R. Bamrick-Fernandez, Allison M. Ariatti, Adam Z. Rawls, Norma B. Ojeda, Barbara T. Alexander Soluble guanylate cyclase stimulation in late gestation does not mitigate asymmetric intrauterine growth restriction or cardiovascular risk induced by placental ischemia in the rat Am J Physiol Heart Circ Physiol, published May 3, 2021. DOI: 10.1152/ajpheart.00033.2021
Can epigenetic analysis of DNA methylation in the myocardial genome be used to evaluate individual differences in response to treatment among heart failure patients? Consulting Editor Dr. Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine) interviews lead author Dr. Adam Wende (University of Alabama at Birmingham, Birmingham) and expert Dr. Bradford Hill (University of Louisville) about the innovative new study by Pepin et al. The authors studied human heart tissue obtained from heart failure patients during left ventricular assist device (LVAD) placement surgery. Wende and co-authors found that one of the strongest signals in the epigenetic mark DNA methylation was differentially regulated by self-reported race, identifying specific patterns in patients who self-identified as either African American or Caucasian. Long term outcomes were found to be significantly worse in the patient cohort self-identified as African American. Can the epigenetic changes uncovered by the authors help explain why African Americans have a higher susceptibility to heart failure? Listen and find out.
Mark E. Pepin, Chae-Myeong Ha, Luke A. Potter, Sayan Bakshi, Joseph P. Barchue, Ayman Haj Asaad, Steven M. Pogwizd, Salpy V. Pamboukian, Bertha A. Hidalgo, Selwyn M. Vickers, Adam R. Wende Racial and socioeconomic disparity associates with differences in cardiac DNA methylation among men with end-stage heart failure Am J Physiol Heart Circ Physiol, published May 7, 2021. DOI: doi.org/10.1152/ajpheart.00036.2021
As we uncover in our latest podcast episode, a meta-analysis of multiple RNA sequencing datasets with different data types leads to truly novel insights. Listen as Consulting Editors Ganesh Halade (University of South Florida) and Taben Hale (University of Arizona) interview authors Adam Engler and Alex Whitehead (University of California, San Diego) about their unique meta-analysis of RNA sequencing data which compared postnatal day 1 and day 8 hearts post-MI. The authors identified two distinct data clusters—an infarct cluster and a sham control cluster—and identified 37 genes which are critically involved in connecting fibroblasts to macrophages in the cardiac remodeling process. Because the authors did not take an either/or approach, and instead focused on both macrophages and fibroblasts, their meta-analysis connected the dots between inflammation and scar formation gene networks. “I think this is a very good example of the sum being greater than the parts,” explained Engler. This innovative work highlights several specific inflammatory processes critical to post-MI remodeling. What cellular and molecular pathways do the authors think should be targeted for therapeutic success? Listen and learn more.
Alexander J. Whitehead and Adam J. Engler Regenerative Crosstalk between Cardiac Cells and Macrophages Am J Physiol Heart Circ Physiol, published March 26, 2021. DOI: doi.org/10.1152/ajpheart.00056.2021
What do an undergraduate degree in history, the transcription factor Forkhead box class O1 (FoxO1), and maternity leave have in common? In this new episode of our Behind the Bench podcast, host Lisandra de Castro Bras (East Carolina University) and her new co-host Charlotte Usselman (McGill University) interview lead author Kate Weeks (Baker Heart and Diabetes Institute) about a new study by Weeks and co-authors which shows FoxO1 is a critical mediator of exercise-induced cardiac hypertrophy. We reached out to Kate to get the story behind her research, because we know how critically important it is for women scientists to hear from other women scientists about balancing scientific research and life outside the lab. Kate discusses the implications of her study in considering FoxO1 as a target for treating heart disease, and she also discusses the implications of maternity leave on maintaining her career as a research scientist. Interspersed in this engaging and enlightening conversation about Kate’s research are life lessons about planning your career path, taking family leave from work, inquiring about childcare at conferences, and so much more. Listen now.
Kate L. Weeks,Yow Keat Tham, Suzan G. Yildiz, Yonali Alexander, Daniel G. Donner, Helen Kiriazis, Claudia A. Harmawan, Amy Hsu, Bianca C. Bernardo, Aya Matsumoto, Ronald A. DePinho, E. Dale Abel, Elizabeth A. Woodcock, Julie R. McMullen FoxO1 is required for physiological cardiac hypertrophy induced by exercise but not by constitutively active PI3K Am J Physiol Heart Circ Physiol, published April 7, 2021. DOI: doi.org/ 10.1152/ajpheart.00838.2020
What is the effect of vascular function in the pathogenesis of Inflammatory Bowel Disease (IBD)? According to Centers for Disease Control data, there are approximately 3 million people with IBD in the U.S. population, with more than 7,000 new cases of IBD diagnosed every year. IBD patients are at greater risk for developing cardiovascular disease compared to age-matched peers. Listen as Consulting Editor Camilla Wenceslau (University of Toledo) interviews senior author Erika Boerman (University of Missouri) and expert Pooneh Bagher (Texas A&M Health Science Center) about this novel study by Norton et al. Decreased blood flow to the gut is a diagnostic hallmark of IBD, and sensory neurotransmitters calcitonin gene-related peptide (CGRP) and substance P are considered biomarkers of IBD. Using pressure myography to study mesenteric arteries in an interleukin-10 knockout mouse model, Boerman and collaborators investigated the activation of perivascular sensory nerves, which control gastrointestinal tract blood flow. When Boerman and co-authors first blocked substance P receptors and then stimulated sensory nerves, sensory vasodilation was rescued in the IBD vessels. A surprising finding was that the substance P pathway seemed to interfere with the CGRP pathway, preventing normal sensory vasodilation. Does Boerman estimate that an influx of immune cells into the gut, interacting with sensory neurotransmitters, is a factor in IBD pathogenesis? Listen as these experts discuss the mechanisms that impact reduced blood flow and tissue ischemia which leads to IBD, and the unanswered questions which may help to unravel the link between IBD and cardiovascular disease.
Charles E. Norton, Elizabeth A. Grunz-Borgmann, Marcia L. Hart, Benjamin W. Jones, Craig L. Franklin, Erika M. Boerman Role of perivascular nerve and sensory neurotransmitter dysfunction in inflammatory bowel disease Am J Physiol Heart Circ Physiol, published April 22, 2021. DOI: doi.org/10.1152/ajpheart.00037.2021
Does inorganic arsenic in drinking water lead to cardiac hypertrophy? In this episode, host Dominic Del Re (Rutgers New Jersey Medical School) interviews lead author Mark Kohr (Johns Hopkins University) and expert Nicole Purcell (Huntington Medical Research Institutes) about the new study by Kohr and colleagues, which studied the effects of an environmentally-relevant level of inorganic arsenic in the drinking water of male and female mice. Kabir et al were inspired by the public health crisis in Bangladesh caused by arsenic contaminated drinking water. In their study the authors found increased systolic blood pressure, increased LV mass and wall thickness, and induction of the fetal gene program in male mice, but not in female mice. Kohr and co-authors found arsenic promoted calcineurin NFAT signaling but did not disrupt nitric oxide-dependent mechanisms of cardioprotection. The authors uncover sex differences in the cardiovascular response to arsenic, as well as a clear mechanistic link between this environmental risk factor – arsenic in drinking water – and cardiac pathology. Can this work be translated on a larger scale to inspire everyday interventions to mitigate adverse environmental effects on human heart health? To find out, listen now.
Raihan Kabir, Prithvi Sinha, Sumita Mishra, Obialunanma V. Ebenebe, Nicole Taube, Chistian U. Oeing, Gizem Keceli, Rui Chen, Nazareno Paolocci, Ana Rule, Mark J. Kohr Inorganic arsenic induces sex-dependent pathological hypertrophy in the heart Am J Physiol Heart Circ Physiol, published March 24, 2021. DOI: 10.1152/ajpheart.00435.2020