AJP-Heart and Circulatory Physiology Podcast

Immune Cell β2-Adrenergic Receptor in the Heart

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

Estradiol and Endothelin Receptors

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

Left Ventricular Dyssynchrony in Young Bodybuilders

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

Behind the Bench Episode 10

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

Behind the Bench Episode 9

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

Txnip C247S Mutation Improves Cardiac Function in Diabetes

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

Maternal Vaping Impairs Vascular Function in the Offspring

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

Vascular Reactivity in High Fat Fed Dahl SS

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

Testosterone and Exercise in Middle-to-Older Aged Men

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

Soluble Guanylate Cyclase, Intrauterine Growth Restriction, and Cardiovascular Risk

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