AJP-Heart and Circulatory Physiology Podcast

Heterogeneous Sodium in Ventricular Myocytes

Is sodium evenly or unevenly distributed in the subsarcolemmal space? Intracellular sodium is an important regulator of cardiac contractility and plays a role in cardiac arrythmias. Therefore, understanding how and why sodium may be differentially distributed in the subsarcolemmal space is critically important. Associate Editor Mario Delmar (New York University) interviews lead author Jonas Skogestad (University of Oslo) and content expert Sand Despa (University of Kentucky) about the novel studies by Skogestad et al. Using both patch-clamping and mathematical modeling, Skogestad and co-authors challenge the current paradigm by suggesting that subsarcolemmal sodium may exist in not just one, but rather many, compartments. The authors found that, after activating the sodium channel for a short amount of time, the sodium released into the subsarcolemmal space did not affect Na+/K+-ATPase (NKA) activity. Did the same hold true for longer activation times, and what does this indicate about the possible interaction between the sodium pump and sodium channels? Listen now.

 

Jonas Skogestad, Glenn Terje Lines, William E. Louch, Ole M. Sejersted, Ivar Sjaastad, and Jan Magnus Aronsen Evidence for heterogeneous subsarcolemmal Na+ levels in rat ventricular myocytes Am J Physiol Heart Circ Physiol, published January 18, 2019. DOI: 10.1152/ajpheart.00637.2018

Mitochondrial Oxidative Stress in Smoking and Hypertension

Tobacco smoking is still a major global public health risk, despite the well-known facts that smoking increases the risk of cardiovascular disease and hypertension. What is the mechanism by which tobacco smoking induces mitochondrial oxidative stress? Editor-in-Chief Irving H. Zucker (University of Nebraska Medical Center) interviews lead author Sergey Dikalov (Vanderbilt University Medical Center) and content expert Andreas Beyer (Medical College of Wisconsin) about the new study by Dikalov et al that uses a unique chronic tobacco smoking model in both human and animal tissues to determine that smoking induces oxidation of mitochondrial cardiolipins. Dikalov and co-authors performed novel catalase experiments to show that smoking interferes with cell signaling pathways, and that specific scavenging of mitochondrial catalase can prevent alterations of vascular functions. Short-term (just 2 weeks!) of tobacco smoking showed marked reductions in SIRT3, which is a key mitochondrial deacetylase and a marker of longevity. Did smoking cessation return SIRT3 to normal healthy levels? Listen and learn.

 

Sergey Dikalov, Hana Itani, Bradley Richmond, Aurelia Vergeade, S. M. Jamshedur Rahman, Olivier Boutaud, Timothy Blackwell, Pierre P. Massion, David G. Harrison, and Anna Dikalova Tobacco smoking induces cardiovascular mitochondrial oxidative stress, promotes endothelial dysfunction, and enhances hypertension Am J Physiol Heart Circ Physiol, published February 27, 2019. DOI: 10.1152/ajpheart.00595.2018

Vasoconstriction in White and Brown Adipose

How is adipose tissue vascular reactivity impacted by obesity? Editor in Chief Irving H. Zucker (University of Nebraska Medical Center) interviews lead author Lisa Lesniewski (University of Utah) and content expert Camilla Wenceslau (University of Toledo) about this central question in the new study by Hazra et al. To explore the differential activity of feed arteries from both white and brown adipose tissue to important vasoconstrictors, Lesniewski and co-authors used a pressure myography system to examine vasoreactivity in excised feed arteries from normal and high-fat diet fed mice. Despite greater non-receptor mediated vasoconstriction in arteries from brown adipose tissue, the authors did not find an increase in receptor mediated vasoconstriction in brown adipose tissue compared to white adipose tissue. In general, Lesniewski and colleagues found that a high-fat diet lowered reactivity to the receptor-mediated agonists. Could stimulating blood flow in the vasculature of brown adipose tissue have clinical implications for fighting the obesity epidemic? Listen and learn more.

 

Sugata Hazra, Grant D. Henson, R. Colton Bramwell, Anthony J. Donato, and Lisa A. Lesniewski Impact of high-fat diet on vasoconstrictor reactivity of white and brown adipose tissue resistance arteries Am J Physiol Heart Circ Physiol, published February 12, 2019. DOI: 10.1152/ajpheart.00278.2018

HIF1 Regulates miR-29c and SERCA2

How does HIF1 regulate microRNAs in the heart? This is the question we explore in our latest podcast. Listen as Associate Editor Junichi Sadoshima (Rutgers New Jersey Medical School) interviews authors Ralph Shohet and Allison Williams (both of University of Hawaii), along with content expert Asa Gustafsson (University of California-San Diego), about the intriguing new work by Williams et al. It is known that miR-29c is a critical mediator of HIF1 for downregulation of SERCA2, which is commonly seen in heart failure. Using a tetracycline-inducible transgenic mouse model with an oxygen-stable form of HIF, the authors observed deeper levels of HIF action in the heart. What consequences of stable HIF1 activation did the authors uncover? How closely does isolated HIF expression mimic authentic ischemia? Listen and find out.

 

Allison Lesher Williams, Chad B. Walton, Abigail Avelar, and Ralph Victor Shohet HIF-1 regulation of miR-29c impairs SERCA2 expression and cardiac contractility Am J Physiol Heart Circ Physiol, published February 20, 2019. DOI: 10.1152/ajpheart.00617.2018

MRGD Deficiency Leads to Dilated Cardiomyopathy

What are the cardiac effects of genetic deletion of the alamandine peptide receptor MRGD? Listen as Associate Editor Debra Diz (Wake Forest University School of Medicine) interviews lead author Robson Santos (Universidade Federal De Minas Gerais, Brazil) and content expert Michelle Parvatiyar (Florida State University) about the innovative work by Oliveira et al. Santos and co-authors found that genetic deletion of MRGD in mice triggered the development of severe dilated cardiomyopathy in the absence of hypertension. Robson and colleagues found several key phenotypic changes—increased adiposity chief among them—but no changes in blood pressure in the MRGD knockout mice. Surprisingly the authors found a decrease in ANP expression, leading them to consider ANP key to the pathogenesis of the cardiac dysfunction in this animal model. Don’t miss the behind-the-scenes story of how alamandine got its unique name. Listen now.

 

Aline Cristina Oliveira, Marcos Barrouin Melo, Daisy Motta-Santos, A Augusto Peluso, Fernando Souza-Neto, Rafaela F da Silva, Jonathas FQ Almeida, Giovanni Canta, Adelina M. Reis, Gleisy Goncalves, Gabriela G Cerri, Danielle Coutinho, Itamar Couto Guedes de Jesus, Silvia Guatimosim, Natalia D Linhares, Natalia Alenina, Michael Bader, Maria José Campagnole-Santos, and Robson A. Souza Santos Genetic deletion of the alamandine receptor MRGD leads to dilated cardiomyopathy in mice Am J Physiol Heart Circ Physiol, published January 8, 2019. DOI: 10.1152/ajpheart.00075.2018

Differential Control of Sympathetic Outflow in Young Humans

What drives variability in muscle sympathetic nerve activity among healthy individuals? Associate Editor Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine) explores this central question in a new interview with lead author Philip Millar (University of Guelph) and content expert Craig Steinback (University of Alberta) about the work by Incognito et al. Millar and co-authors identified subpopulations within muscle sympathetic single unit nerve fibers that display opposite responses to typical sympathoexcitatory stressors-- lower body negative pressure and an exercise stimulus. The authors uncovered that we can recruit, and de-recruit, individual muscle sympathetic nerve fibers in response to these stressors. What are the potential clinical implications for patients with orthostatic intolerance or hypertension? Listen to find out.

 

Anthony V. Incognito, Connor J. Doherty, Massimo Nardone, Jordan B. Lee, Karambir Notay, Jeremy D. Seed, and Philip J. Millar Evidence for differential control of muscle sympathetic single units during mild sympathoexcitation in young, healthy humans Am J Physiol Heart Circ Physiol, published December 17, 2018. DOI: 10.1152/ajpheart.00675.2018

Personalized Medicine in HFpEF

Why is biological phenotyping needed to improve current clinical treatment of heart failure with preserved ejection fraction (HFpEF)? Listen as Guest Editor Maria Bloksgaard (University of Southern Denmark) interviews lead author Vanessa van Empel (Maastricht University Medical Centre) and content expert Nicholas Houstis (Massachusetts General Hospital) about the new Review by Barandiarán Aizpurua et al, which points out that if we want to develop more personalized HFpEF treatments, we need greater understanding of the underlying pathophysiology of HFpEF. Can animal models of HFpEF “match” clinical phenotypes and accurately mimic exercise intolerance, congestive heart failure, and cardiovascular death experienced by HFpEF patients? Listen now and find out.

 

Arantxa Barandiarán Aizpurua, Blanche Schroen, Marc van Bilsen, and Vanessa P. M. van Empel Targeted HFpEF therapy based on matchmaking of human and animal models Am J Physiol Heart Circ Physiol, published September 21, 2018. DOI: 10.1152/ajpheart.00024.2018

Statistical Considerations in Reporting Cardiovascular Research

“As biomedical scientists, we have an obligation to get the numbers right,” declares AJP-Heart and Circulatory Physiology Editor-in-Chief Dr. Irving H. Zucker in the opening of this insightful discussion on, that’s right, statistics. This isn’t your run-of-the-mill boring lecture on statistics, however. Listen as Irv Zucker (University of Nebraska Medical Center) interviews authors Merry L. Lindsey (University of Mississippi Medical Center), Gillian A. Gray (University of Edinburgh), Susan K. Wood (University of South Carolina School of Medicine), and Douglas Curran-Everett (National Jewish Health) about their new Guidelines in Cardiovascular Research article that provides clear, useful, and approachable guidance to authors and reviewers for reporting statistics in cardiovascular research. The authors discuss reporting precise p-values, using standard deviation rather than standard error, and looking beyond the t-test to more detailed analyses and visualization tools for processing datasets. This podcast is full of sage advice about planning statistical considerations early in the study design phase. “Being proactive rather than reactive will make the study stronger,” noted Merry Lindsey. Listen now for more from these experts.

 

Merry L. Lindsey, Gillian A. Gray, Susan K. Wood, and Douglas Curran-Everett Statistical Considerations in Reporting Cardiovascular Research Am J Physiol Heart Circ Physiol, published August 8, 2018. DOI: 10.1152/ajpheart.00309.2018

Unregulated Ca2+ Cycling Exacerbates DMD Cardiomyopathy

Does improving intracellular calcium handling through cardiac-specific phospholamban ablation in a mouse model of Duchenne Muscular Dystrophy affect the development of cardiomyopathy? In this podcast, Associate Editor Junichi Sadoshima (Rutgers New Jersey Medical School) interviews first author Michelle Law (University of Minnesota) and content expert Sakthivel Sadayappan (University of Cincinnati) about the new study by Law and co-authors. Using the mdx mouse model, phospholamban ablation was studied in the context of dystrophic cardiomyopathy. Law et al found that although calcium cycling was enhanced in myocytes, DMD cardiomyopathy was surprisingly worsened in vivo. Given that there are both calcium mishandling and mechanical stress components to DMD cardiomyopathy, do the authors suspect that unregulated Serca2a pump function damaged the sarcolemma and increased fibrosis and myocyte death? Listen and find out.

 

Michelle L Law, Kurt W Prins, Megan E Olander, and Joseph M Metzger Exacerbation of dystrophic cardiomyopathy by phospholamban deficiency-mediated chronically increased cardiac Ca2+ cycling in vivo Am J Physiol Heart Circ Physiol, published August 17, 2018. DOI: 10.1152/ajpheart.00341.2018

Sex Differences in Depression-Like Behavior Post Myocardial Infarction

Nearly one-fifth of heart failure patients develop depression or depression-like symptoms and are therefore at greater risk for additional cardiac events and mortality. Inflammation in the hypothalamus has been shown to play a role in heart failure progression and depression. Is there also a link between the presence, or absence, of estrogens in the brain and heart failure comorbid with depression? In this special extended-length podcast, Associate Editor Kaushik Patel (University of Nebraska Medical Center) interviews senior author Frans H.H. Leenen (University of Ottawa Heart Institute) and content expert Adam Case (University of Nebraska Medical Center). Past clinical studies have clearly shown that post-menopausal women with heart failure are at higher risk for developing depression compared to premenopausal women. Disappointed with previous animal studies performed only in male rats, Leenen and co-authors embarked on designing new animal studies to specifically address sex differences. Najjar et al reported that young female rats were protected from depression by the presence of estrogens, compared to both male rats and post-menopausal female rats. Listen now as our experts discuss these novel studies as well as the interplay of peripheral inflammation, central inflammation, and cardiac sympathetic afferent pathways in the development of depression with heart failure.

 

Fatimah Najjar, Monir Ahmad, Diane Lagace, and Frans H.H. Leenen Sex Differences in Depression-Like Behavior and Neuroinflammation in Rats Post MI: Role of Estrogens Am J Physiol Heart Circ Physiol, published July 27, 2018. DOI: 10.1152/ajpheart.00615.2017