AJP-Heart and Circulatory Physiology Podcast

Prenatal Dexamethasone Alters Female Cardiovascular Function

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

The AJP-Heart and Circ Podcast Special Anniversary Episode #300

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.

GLS1 Inhibition Improves Cardiac Remodeling -- Japanese Language Version

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

GLS1 Inhibition Improves Cardiac Remodeling -- English Language Version

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

Beta1-Adrenergic Receptor Cleavage by Trypsin

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

Murine MI Sizing with 2D and 4D Echocardiography

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

Incorporating Sex as a Biological Variable into Basic and Clinical Research Studies

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

 

Guidelines for in vivo Mouse Models of Myocardial Infarction

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

Behind the Bench Episode 11

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

COVID-19 and Microvascular Function

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