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


Macrophage MMP-9 Accelerates Cardiac Aging

Is macrophage MMP-9 a prime upstream regulator of cardiac aging? Yes, according to new research by Toba et al, explored in our latest podcast. Editor in Chief Irving H. Zucker (University of Nebraska Medical Center) interviews lead author and Deputy Editor Merry Lindsey (University of Mississippi Medical Center) and content expert Richard Gumina (Vanderbilt University) about the work by Lindsey and colleagues, which expands our knowledge of macrophage MMP-9 overexpression and its amplification of the myocyte hypertrophic response to aging. Did Lindsey and co-authors find in their experimental model that diastolic cardiac physiology was impaired before systolic cardiac physiology? MMP-9 appears to be a driver of inflammation, rather than a consequence of inflammation. Does MMP-9 in the aged heart also play a pro-fibrogenic role? Listen and learn more.


Hiroe Toba, Presley L. Cannon, Andriy Yabluchanskiy, Rugmani Padmanabhan Iyer, Jeanine D’Armiento, Merry L. Lindsey Transgenic overexpression of macrophage matrix metalloproteinase-9 exacerbates age-related cardiac hypertrophy, vessel rarefaction, inflammation, and fibrosis Am J Physiol Heart Circ Physiol, published March 1, 2017. DOI:10.1152/ajpheart.00633.2016


Genes and Vascular Reactions to Diving

Is the vascular response in humans to the diving reflex genetically determined? In our first-ever podcast recorded in both Russian and English, Associate Editor Debra I. Diz (Wake Forest University School of Medicine) interviews lead author Tatiana I. Baranova (St.-Petersburg State University, Russia), her translator Vladimir Boykov, and content expert Charles E. Wood (University of Florida). Listen as we explore the work by Baranova and co-authors, which determined that polymorphisms in the bradykinin and renin-angiotensin systems are the driving force behind hemodynamic responses to the diving reflex. What is known about the functional implications of the mutations that affect the coding regions of the genes ADBR2, ACE, AGTR1, BDKRB2, and REN? Does this work on the genomics of hemodymic changes during transient hypoxia have potential therapeutic applications in personalized medicine? Listen to find out.


Tatiana I. Baranova, Dmitrii N. Berlov, Oleg S. Glotov, Ekaterina A. Korf, Alexey D. Minigalin, Alla V. Mitrofanova, Ildus I Ahmetov, Andrey S. Glotov Genetic determination of the vascular reactions in humans in response to the diving reflex Am J Physiol Heart Circ Physiol, published online December 6, 2016. DOI: 10.1152/ajpheart.00080.2016


Sympathetic Nerves and Cardiac Propagation

What are the mechanisms by which sympathetic nerve activity triggers ventricular arrhythmia? Listen as Consulting Editor Crystal Ripplinger (University of California Davis) interviews lead author Olujimi Ajijola (University of California Los Angeles) and content expert Christian Meyer (University Heart Centre Hamburg) about this key question explored in the innovative work by Ajijola et al. In a chronically infarcted porcine model, Ajijola and co-authors investigated whether sympathetic activity modulated activation and conduction in normal hearts and post myocardial infarction. The authors found that right stellate stimulation had a stronger effect than left in normal hearts. Was the same true after myocardial infarction? Do the clinical implications of modulation of late potentials during sympathetic stimulation suggest that clinicians need to rethink their ablation mapping techniques? Listen and learn.


Olujimi A. Ajijola, Robert L Lux, Anadjeet Khahera, OhJin Kwon, Eric Aliotta, Daniel Ennis, Michael C. Fishbein, Jeffrey Laurence Ardell, Kalyanam Shivkumar Sympathetic Modulation of Electrical Activation In Normal and Infarcted Myocardium: Implications for Arrhythmogenesis Am J Physiol Heart Circ Physiol, published online January 13, 2017. DOI: 10.1152/ajpheart.00575.2016


Cerebroarterial Dysfunction in Swedish-Arctic AD Mice

In a true chicken-and-egg question, can researchers accurately pinpoint if cerebrovascular pathology or Alzheimer's disease (AD) present sequentially or simultaneously? Listen as Guest Editor Vincenzo Lionetti (Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy) interviews lead author Mario Merlini (University of Zurich, Switzerland, and Gladstone Institute of Neurological Disease, UCSF) and content expert Roy Weller (University of Southampton School of Medicine) about the novel work by Merlini et al that seeks to untangle the complicated web of cerebrovascular pathology, AD pathology, and vascular dementia, as well as neuronal and endothelial tau pathology. In this extended podcast, we speculate on the role that endothelial tau may play in disrupting nitric oxide synthase in the nucleus. Our experts consider whether endothelial dysfunction at the onset of AD is a gene or age-dependent phenomenon. Why did Merlini and co-authors use histology to investigate the loss of cyclic-GMP in the absence of amyloid deposits in the basilar artery? Does the Swedish-Arctic mouse model accurately reflect the AD clinical condition? Listen to this intriguing conversation and find out.


Mario Merlini, Yi Shi, Stephan Keller, Gianluigi Savarese, Alexander Akhmedov, Rebecca Derungs, Remo D. Spescha, Luka Kulic, Roger M. Nitsch, Thomas F. Lüscher, Giovanni G. Camici Reduced nitric oxide bioavailability mediates cerebroarterial dysfunction independent of cerebral amyloid angiopathy in a mouse model of Alzheimer’s disease Am J Physiol Heart Circ Physiol, published February 1, 2017. DOI: 10.1152/ajpheart.00607.2016