AJP-Heart and Circulatory Physiology Podcasts
GLS1 Inhibition Improves Cardiac Remodeling — Japanese Language Version

GLS1 Inhibition Improves Cardiac Remodeling — Japanese Language Version

April 28, 2022

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

GLS1 Inhibition Improves Cardiac Remodeling — English Language Version

April 28, 2022

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

Beta1-Adrenergic Receptor Cleavage by Trypsin

April 25, 2022

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

Murine MI Sizing with 2D and 4D Echocardiography

April 6, 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

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

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

March 18, 2022

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

Guidelines for in vivo Mouse Models of Myocardial Infarction

March 2, 2022

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

Behind the Bench Episode 11

March 1, 2022

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

COVID-19 and Microvascular Function

February 25, 2022

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

Cortical Bone Stem Cells Effects on Cardiac Wound Healing

Cortical Bone Stem Cells Effects on Cardiac Wound Healing

January 6, 2022

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

New Permeability Assessment of Microvessels-on-a-Chip

New Permeability Assessment of Microvessels-on-a-Chip

December 17, 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

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