EET Intervention on Wnt1, NOV and HO-1 Signaling Prevents Obesity-Induced Cardiomyopathy

Do the well-established beneficial effects of EETs (epoxyeicosatrienoic acids) in the vasculature also extend to the myocardium? That's just what we explore in this new podcast about the work by Cao et al, which is highlighted in our Call for Papers on Heart Failure - Novel Therapeutic Pathways Emerging from Basic Science. Listen as Consulting Editor David D. Gutterman (Medical College of Wisconsin) interviews lead author Nader G. Abraham (New York Medical College) and content expert Kevin Dellsperger (Augusta University Health System) about the translational work by Abraham and colleagues. As a downregulator of NOV, EETs act as anti-inflammatory molecules attenuating cardiac damage. Abraham and co-authors found that EETs increase Wnt, resulting in the reprogramming of epicardial fat toward a brown fat phenotype, thereby increasing left ventricle function and contractility. What novel and "potentially drug-able" pathway is responsible for attenuating obesity-induced cardiomyopathy? Listen now.


Jian Cao, Shailendra P. Singh, John McClung, Gregory Joseph, Luca Vanella, Ignazio Barbagallo, Houli Jiang, John R. Falck, Michael Arad, Joseph I. Shapiro, Nader G. Abraham EET Intervention on Wnt1, NOV and HO-1 Signaling Prevents Obesity-Induced Cardiomyopathy in Obese Mice Am J Physiol Heart Circ Physiol, published June 2, 2017. DOI: 10.1152/ajpheart.00093.2017


Leucine Metabolism Inhibits Cardiac Glucose Uptake

Does the branch chain amino acid leucine mediate cardiac insulin resistance? Listen as Associate Editor Gary Lopaschuk (University of Alberta) interviews lead author Luc Bertrand (Université Catholique de Louvain) and content expert Ravichandran Ramasamy (NYU Langone Medical Center) about the recent work by Renguet et al which investigated whether leucine is simply a biomarker of type 2 diabetes or a factor of the metabolic inflexibility which is a hallmark of type 2 diabetes pathogenesis. Bertrand and colleagues showed that the inhibitory reaction of leucine and ketone bodies in glucose transport requires an increase in protein acetylation, which then contributes to the inhibition of cardiac glucose uptake by hampering the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. This new study by Bertrand and colleagues may be “a new piece in the complex puzzle of cardiac insulin resistance.” Listen and learn more.


Edith Renguet, Audrey Ginion, Roselle Gélinas, Laurent Bultot, Julien Auquier, Isabelle Robillard Frayne, Caroline Daneault, Jean-Louis Vanoverschelde, Christine Des Rosiers, Louis Hue, Sandrine Horman, Christophe Beauloye, Luc Bertrand Metabolism and acetylation contribute to leucine-mediated inhibition of cardiac glucose uptake Am J Physiol Heart Circ Physiol, published online June 23, 2017. DOI: 10.1152/ajpheart.00738.2016


β-AR Stimulation and Alternans in Border Zone Cardiomyocytes

Are calcium alternans in the post-MI border zone more susceptible to the effects of sympathetic stimulation than in normal zone cardiomyocytes? In this podcast Consulting Editor Crystal Ripplinger uncovers the answer in her interview with lead author Jordi Heijman and content expert Thomas Hund about the recent work by Tomek et al. Heijman and co-authors explored sympathetic stimulation and its role in arrhythmogenesis by applying an innovative computational model to the canine post-MI border zone. Did Heijman and colleagues find that β-adrenergic stimulation suppressed alternans by one single mechanism or via multiple pathways? Did Heijman and co-authors also find that hyperinnervation in the border zone is actually anti-arrhythmic, by preventing alternans? Listen and find out.


Jakub Tomek, Blanca Rodriguez, Gil Bub, Jordi Heijman β-adrenergic receptor stimulation inhibits proarrhythmic alternans in post-infarction border zone cardiomyocytes: a computational analysis Am J Physiol Heart Circ Physiol, published online May 26, 2017. DOI: 10.1152/ajpheart.00094.2017


Resveratrol and Exercise Capacity in Heart Failure

Does resveratrol positively impact exercise intolerance in heart failure patients? Listen as Associate Editor Christine Des Rosiers (Universite de Montreal) interviews lead author Jason Dyck (University of Alberta) and content expert Yan Burelle (University of Ottawa) about the exciting new study by Sung et al, which used a mouse model of heart failure to determine if treatment with resveratrol restored exercise tolerance to normal levels. Dyck and co-authors clearly show that resveratrol is effective as a treatment for exercise intolerance in heart failure, not solely as a preventative strategy, and this may have important clinical implications for human heart failure patients. What role does the gut microbiome play in this resveratrol treatment study, and what cautionary words do these experts have about equating nutraceutical resveratrol treatment with the naturally occurring polyphenol resveratrol commonly found in red wine? Listen and find out.


Miranda M. Sung, Nikole J Byrne, Ian M Robertson, Ty T Kim, Victor Samokhvalov, Jody Levasseur, Carrie-Lynn M Soltys, David Fung, Neil Tyreman, Emmanuel Denou, Kelvin Jones, John M Seubert, Jonathan D. Schertzer, Jason R.B. Dyck Resveratrol improves exercise performance and skeletal muscle oxidative capacity in heart failure Am J Physiol Heart Circ Physiol, published April 1, 2017. DOI: 10.1152/ajpheart.00455.2016


Exosomes in Pediatric Dilated Cardiomyopathy

Are circulating exosomes in serum derived from pediatric patients with dilated cardiomyopathy modulating the phenotype of cardiomyocytes and causing a pathological response in cells? Yes, according to a novel and technically-challenging in vitro study by Jiang et al. Listen as Guest Editor Sumanth Prabhu (University of Alabama at Birmingham) interviews lead author Carmen (Kika) Sucharov (University of Colorado Denver) and David D. Gutterman (Medical College of Wisconsin), content expert and Consulting Editor. Exosomes are small vesicles present in cells and released into the circulation carrying both coding and noncoding RNAs, as well as proteins and lipids. The study by Sucharov and co-authors seeks to further elucidate the unique features of the pathophysiology of heart failure in children. Does this study also provide a roadmap for future research into the “culprit component” of exosomes responsible for the phenotypic change shown in cardiomyocytes by the Sucharov lab? Listen and learn more.


Xuan Jiang, Juliana Sucharov, Brian L. Stauffer, Shelley D. Miyamoto, Carmen C. Sucharov Exosomes from pediatric dilated cardiomyopathy patients modulate a pathological response in cardiomyocytes Am J Physiol Heart Circ Physiol, published April 1, 2017. DOI: 10.1152/ajpheart.00673.2016


Exercise Averts High Pressure-Induced Vascular Dysfunction

Can chronic exercise prevent endothelial damage that occurs to the arterioles because of acute increases in arterial pressure? Consulting Editor David Gutterman (Medical College of Wisconsin) interviews lead author Austin Robinson (University of Delaware) and content expert Lisa Lesniewski (University of Utah) about this very question in our latest podcast. Using a unique animal model comparing sedentary mice to mice who voluntarily ran 6 km per day, Robinson and co-authors found that NADPH oxidase and angiotensin II were responsible for impaired flow-induced dilation following high pressure stress in arterioles removed from the “couch potato” mice but not in exercised mice. Why did the authors choose to study resistance artery function in subcutaneous adipose tissue, compared to visceral adipose tissue? What are the implications for maintaining cardiovascular fitness, and how long does a bout of exercise need to last to confer the vasculoprotective effects? Listen and find out.


Austin T. Robinson, Ibra S. Fancher, Varadarajan Sudhahar, Jing Tan Bian, Marc D. Cook, Abeer M. Mahmoud, Mohamed M. Ali, Masuko Ushio-Fukai, Michael D. Brown, Tohru Fukai, Shane A. Phillips Short-term regular aerobic exercise reduces oxidative stress produced by acute in the adipose microvasculature Am J Physiol Heart Circ Physiol, published May 1, 2017. DOI: 10.1152/ajpheart.00684.2016


Gestational Nanomaterial Exposure and Cardiac Dysfunction

Does exposure when pregnant to the nanomaterial titanium dioxide have an impact on progeny? Listen as Associate Editor Gary Lopaschuk (University of Alberta) interviews lead author John Hollander (West Virginia University School of Medicine) and content expert John Ussher (University of Alberta) about the recent study by Hathaway et al., which used a gestational animal model to determine if acute exposure to the nanomaterial titanium dioxide would affect fetal cardiac contractile function and bioenergetics. Hollander and co-authors found that bioenergetics are negatively impacted, which ultimately affected whole heart function and myocyte function in young adult animals. Since it is well known that metabolic enzymes and regulators of mitochondrial function are subject to epigenetic alterations, do the authors speculate that epigenetic modifications may play a role in the phenotype they observed? With engineered nanomaterials appearing in numerous commercial applications—from toothpaste to ceramic tiles—what other nanoparticles are important to study for potential short and long-term effects on progeny? Listen and find out.


Quincy A. Hathaway, Cody E. Nichols, Danielle L. Shepherd, Phoebe A. Stapleton, Sarah L. McLaughlin, Janelle C. Stricker, Stephanie L. Rellick, Mark V. Pinti, Alaeddin B. Abukabda, Carroll R. McBride, Jinghai Yi, Seth M. Stine, Timothy R. Nurkiewicz, John M. Hollander Maternal-engineered nanomaterial exposure disrupts progeny cardiac function and bioenergetics Am J Physiol Heart Circ Physiol, published March 1, 2017. DOI: 10.1152/ajpheart.00634.2016


Interval Exercise and Flow-mediated Dilation

Does high-intensity interval training (HIIT) have any effects on blood vessel function in type 2 diabetes patients? In this engaging podcast, Consulting Editor Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine) interviews lead author Jonathan Little (University of British Columbia Okanagan) and content expert Ellen Dawson (Liverpool John Moores University) about the exciting new exercise training study by Francois et al. Little and co-authors compared a cardio-type HIIT workout of cycling to a resistance exercise HIIT workout, in both type 2 diabetes patients and healthy age-matched master athletes. Did the authors find the resistance HIIT was more effective at improving flow mediated dilation and endothelial function in type 2 diabetes (T2D) patients? The results of this study are consistent with a shift to considering T2D a vascular disease, and suggest that HIIT may be a practical exercise strategy for improving vascular function in T2D patients. Furthermore, could resistance-based HIIT solve the very real issue of patient compliance? After all, says Dawson, "We need people to be exercising, and the best kind of exercise is the one that they're going to continue to do."


Monique E. Francois, Cody Durrer, Kevin J. Pistawka, Frank A. Halperin, Jonathan P. Little Resistance-based interval exercise acutely improves endothelial function in type 2 diabetes Am J Physiol Heart Circ Physiol, published November 1, 2016. DOI: 10.1152/ajpheart.00398.2016


Guidelines for Measuring Sympathetic Nerve Activity

What are the best technological and methodological guidelines for measuring sympathetic nerve activity in humans and animals? In this *special edition* podcast, Editor in Chief Irving H. Zucker (University of Nebraska Medical Center) interviews lead authors, and leading experts, Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine), Jason Carter (Michigan Technological University), Geoffrey Head (Baker IDI Heart and Diabetes Institute), and John Osborn (University of Minnesota) about this comprehensive tour de force article of Guidelines in Cardiovascular Physiology by Hart et al. Bringing together nine global experts to collaborate and build a consensus on best practices for measuring SNA took over a year to accomplish, and the Editors of AJP-Heart and Circ are both exceptionally grateful to the authors and proud to publish this guidelines article –the first of its kind for the journal! Listen as Jason Carter and Nisha Charkoudian discuss human microneurography, the main validation techniques and the potential pitfalls to recording multi-unit and single unit activity. Continue listening as John Osborn and Geoff Head discuss optimal sympathetic recording techniques in experimental animals, the “do’s and don’ts” of recording SNA in conscious animals, surgical techniques needed, and avoiding artifactual data. This conversation is unlike any other podcast in cardiovascular journals. Don’t miss the opportunity to hear these experts discuss their work, their collaboration, and the net result—comprehensive guidelines for measuring sympathetic nerve activity. Listen now.


Emma C. J. Hart, Geoffrey A Head, Jason R. Carter, Gunnar Wallin, Clive N May, Shereen M Hamza, John E. Hall, Nisha Charkoudian, John W. Osborn Recording sympathetic nerve activity in conscious humans and other mammals: guidelines and the road to standardization Am J Physiol Heart Circ Physiol, published March 31, 2017. DOI: 10.1152/ajpheart.00703.2016


Anti-arrhythmic Mechanism of Bilateral Stellectomy

What exactly is cardiac denervation, and can it have an anti-arrhythmic effect in the setting of chronic myocardial infarction? Listen as Associate Editor Mario Delmar (New York University) interviews lead author Marmar Vaseghi (UCLA Cardiac Arrhythmia Center) and Consulting Editor and content expert Crystal Ripplinger (University of California, Davis) about this translational study by Vaseghi and colleagues, which used a porcine model to determine if bilateral cardiac sympathetic denervation reduced ventricular tachy-arrhythmia inducibility in both normal and infarcted hearts. What are the possible short-term and long-term changes in the regulation of the inotropic response resulting from the denervation? What are the cellular mechanisms responsible for changes in action potential durations? Listen to find out.


Tadanobu Irie, Kentaro Yamakawa, David Hamon, Keijiro Nakamura, Kalyanam Shivkumar, Marmar Vaseghi Cardiac sympathetic innervation via middle cervical and stellate ganglia and antiarrhythmic mechanism of bilateral stellectomy Am J Physiol Heart Circ Physiol, published March 1, 2017. DOI: 10.1152/ajpheart.00644.2016