Cardiac Mineralocorticoid Receptors Diastolic Dysfunction

What role does a “Western diet” –one largely centered around high fat and high fructose corn syrup intake—play in the metabolic syndrome of insulin resistance, diabetes, and obesity? Deputy Editor Dr. Merry Lindsey (University of Mississippi Medical Center) interviews first author Dr. Brian Bostick (University of Missouri) and content expert Dr. Nikolaos Frangogiannis (Albert Einstein College of Medicine) in this latest podcast exploring the unique bedside-to-bench work by Bostick and colleagues. Using the recent TOPCAT trial as a springboard, Bostick and co-authors examined whether spironolactone had any beneficial effects on mice with obesity and over-nutrition induced diastolic dysfunction. Listen as we explore how treatment with spironolactone affected M1 and M2 macrophages differently. With more than half of heart failure patients admitted to hospitals today suffering from diastolic dysfunction, does spironolactone have promising therapeutic applications related to obesity and cardiac function?

Brian Bostick, Javad Habibi, Vincent G. DeMarco, Guanghong Jia, Timothy L. Domeier, Michelle D. Lambert, Annayya R. Aroor, Ravi Nistala, Shawn B. Bender, Mona Garro, Melvin R. Hayden, Lixin Ma, Camila Manrique Acevedo, James R. Sowers Mineralocorticoid Receptor Blockade Prevents Western Diet-induced Diastolic Dysfunction in Female Mice Am J Physiol Heart Circ Physiol, published online March 7, 2015, doi: 10.1152/ajpheart.00898.2014.

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Cardiac Steatosis Potentiates Angiotensin II Effects in the Heart

How does the fatty heart—clinically known as cardiac steatosis—respond to other stimuli, like hypertension? In this podcast, Associate Editor Ajay Shah (King's College London) interviews lead author Denis Glenn (University of California San Francisco) and content expert Hemal Patel (University of California San Diego) about the intriguing work by Glenn and colleagues which used angiotensin II as a proxy for hypertension in a mouse model of cardiac steatosis to study the mechanisms behind the increased sensitivity to angiotensin and the effect on fibrosis and heart function. Listen as we weave together the concepts of a “double-hit” disease model, lipid levels and their potential effects on Ang II receptor signaling, and of course, an 18th Century reference to cor adiposum and its modern day equivalent—fatty deposition in the heart. How can this work be translated to the clinic? Listen and learn.

Denis J. Glenn, Michelle C. Cardema, Wei Ni, Yan Zhang, Yerem Yeghiazarians, Dmitry Grapov, Oliver Fiehn, David G. Gardner Cardiac Steatosis Potentiates Angiotensin II Effects in the Heart Am J Physiol Heart Circ Physiol, published February 15, 2015. DOI: 10.1152/ajpheart.00742.2014.

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Redox and Contractility in Diabetic Heart Trabeculae

Given that the current paradigm of diabetic cardiomyopathy is characterized by, among other factors, profoundly altered energy substrate metabolism, how can we interpret the apparently paradoxical beneficial effects of the fatty acid palmitate on diabetic hearts? In this podcast Associate Editor Fabio Recchia (Temple University and Scuola Superiore S. Anna, Pisa) interviews lead author Sonia Cortassa (Johns Hopkins University) and content expert Ethan Anderson (East Carolina University) about the work by Bhatt et al, which investigated the improved contractile performance due to palmitate in diabetic trabeculae under high glucose conditions. That said, is the beneficial effect of fatty acids on the work performed by those muscles dependent on redox levels and energy demand? Listen and find out.

Niraj M. Bhatt, Miguel A. Aon, Carlo G. Tocchetti, Xiaoxu Shen, Swati Dey, Genaro Ramirez-Correa,
Brian O′Rourke, Wei Dong Gao, Sonia Cortassa
Restoring redox balance enhances contractility in heart trabeculae from type 2 diabetic rats exposed to high glucose Am J Physiol Heart Circ Physiol, published February 15, 2015. DOI: 10.1152/ajpheart.00378.2014.

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Pressure-Induced Endothelial Dysfunction

Is upregulation of local generation of angiotensin II in arteries causing the loss of endothelium-dependent dilation in response to short-term increases in blood pressure? Associate Editor Nancy Kanagy (University of New Mexico) interviews lead author Nicholas Flavahan (Johns Hopkins University) and content expert Gregory Fink (Michigan State University) about the insightful work by Flavahan and colleagues that seeks to disentangle the complicated cause-and-effect relationship between the renin-angiotensin system and high blood pressure. So what’s the bottom line? Are acute, however brief, increases in blood pressure bad for our arteries? Listen and learn.

Yingzi Zhao, Sheila Flavahan, Susan W. Leung, Aimin Xu, Paul M. Vanhoutte, Nicholas A. Flavahan Elevated pressure causes endothelial dysfunction in mouse carotid arteries by increasing local angiotensin signaling Am J Physiol Heart Circ Physiol, published February 15, 2015. DOI: 10.1152/ajpheart.00775.2014.

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Aging, Endothelial Dysfunction and SIRT1 Activation

We all know that aging is associated with a loss in vascular endothelial function, but what role does the SIRT1 system play in aiding aging-related processes, such as increased superoxide production and oxidant stress? In this podcast Consulting Editor Michael Wolin interviews lead author Lindsey Gano (University of Colorado, Denver) and content expert Zvonimir Katusic (Mayo Clinic) about the work by Gano et al which used the SIRT1 activator SRT1720 in aging mice to study the effects on endothelium-dependent dilation through COX-2 mediated dilation. Did the authors find a reduction in oxidative stress and inflammation? Listen and learn.

Lindsey B. Gano, Anthony John Donato, Hamza M. Pasha, Christopher M. Hearon Jr., Amy L. Sindler, Douglas R. Seals The SIRT1 activator SRT1720 reverses vascular endothelial dysfunction, excessive superoxide production, and inflammation with aging in mice  Am J Physiol Heart Circ Physiol, published December 15, 2014. DOI: 10.1152/ajpheart.00377.2014.

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Diet, Sex and Exercise in Mice

Do you need to change your New Year’s dieting resolution? Maybe…according to a new study by Konhilas et al, who looked at the trifecta of soy-based versus casein-based diets, exercise, and sex differences in mice. In this engaging new podcast, Deputy Editor Merry L. Lindsey (University of Mississippi Medical Center) interviews lead author John Konhilas (University of Arizona) and expert Ganesh Halade (University of Alabama at Birmingham) about the complex work by Konhilas and colleagues which layered sex dimorphisms in exercise ability, over adaptation to disease and different elements of diet. Did the authors' waterfall of experiments show that diet and sex interact in an overall response to exercise? Listen now.

John P. Konhilas, Hao Chen, Elizabeth D. Luczak, Laurel A. McKee, Jessica Regan, Peter A. Watson, Brian L. Stauffer, Zain I. Khalpey, Timothy A. McKinsey, Todd R. Horn, Bonnie LaFleur, Leslie A. Leinwand Diet and sex modify exercise and cardiac adaptation in the mouse Am J Physiol Heart Circ Physiol, published January 15, 2015. DOI: 10.1152/ajpheart.00532.2014.

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Metabolic Syndrome and Microvessel Density

What is causing vascular rarefaction in the skeletal muscle of patients with metabolic syndrome? In this podcast Associate Editor Gary Lopaschuk (University of Alberta) interviews lead author Jeff Frisbee (West Virginia University) and expert Victor Samokhvalov (University of Alberta) about the work by Frisbee and colleagues, which found that the chronic reduction in vascular nitric oxide bioavailability accompanying metabolic syndrome did not match the development of the rarefaction in skeletal muscle microcirculation. Using a multivariate discriminant model and leaning heavily on the concept of temporal resolution, the authors show that thromboxane and the inflammatory pathway may be the key mechanism for the initial pulse of vascular rarefaction. What potential therapeutic pathways does this open up? Listen now.

Jefferson C. Frisbee, Adam G. Goodwill, Stephanie J. Frisbee, Joshua T. Butcher, Robert W. Brock, I. Mark Olfert, Evan R. DeVallance, Paul D. Chantler Distinct temporal phases of microvascular rarefaction in skeletal muscle of obese Zucker rats Am J Physiol Heart Circ Physiol, published December 15, 2014. DOI: 10.1152/ajpheart.00605.2014.

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Increased Intraluminal Pressure Changes Mechanism of Flow-Mediated Dilation

Why are the endothelial-derived contributors to flow-mediated dilation important to humans with vascular disease? Listen as Associate Editor Debra Diz (Wake Forest School of Medicine) interviews lead author Andreas Beyer (Medical College of Wisconsin) and expert Jennifer Pollock (University of Alabama at Birmingham) about the innovative new work by Beyer et al, which shows that an acute stress response in the human vasculature changes the mechanism of dilation from cardioprotective nitric oxide to pro-atherosclerotic hydrogen peroxide after exposure to increased intraluminal pressure. What do the authors speculate is mediating the “switch” from NO to H2O2, and how do pre-existing conditions, such as systemic hypertension, complicate the stress response mechanism? Listen to find out.

Andreas M. Beyer, Matthew J. Durand, Joseph Hockenberry, T. Clark Gamblin, Shane A. Phillips, David D. Gutterman An acute rise in intraluminal pressure shifts the mediator of flow-mediated dilation from nitric oxide to hydrogen peroxide in human arterioles Am J Physiol Heart Circ Physiol, published December 1, 2014. DOI: 10.1152/ajpheart.00557.2014.

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Circulating FGF23 Levels in Heart Failure

Have Imazu et al discovered a new clinical biomarker for predicting renal dysfunction in heart failure patients? In this engaging podcast Associate Editor Leon De Windt interviews lead author Masafumi Kitakaze (National Cerebral and Cardiovascular Center, Japan) and expert Thomas Thum (Hannover Medical School, Germany) about the pioneering work by Kitakaze and colleagues, which investigated the correlation between circulating FGF23 in non-ischemic patients with early chronic kidney disease and higher incidences of heart failure hospitalization in these patients. How did inflammation, ischemic conditions, gender, age, and other medications influence circulating FGF23 levels? Listen now.

Miki Imazu, Hiroyuki Takahama, Hiroshi Asanuma, Akira Funada, Yasuo Sugano, Takahiro Ohara, Takuya Hasegawa, Masanori Asakura, Hideaki Kanzaki, Toshihisa Anzai, Masafumi Kitakaze Pathophysiological Impact of Serum Fibroblast Growth Factor 23 in Patients with Non-ischemic Cardiac Disease and Early Chronic Kidney Disease Am J Physiol Heart Circ Physiol, published November 15, 2014. DOI: 10.1152/ajpheart.00331.2014.

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Exercise Training Improves Metabo and Mechanoreflex Control in Heart Failure

The so called “exercise pressor reflex” is enhanced in chronic heart failure and drives sympathetic nerve activity during exercise. While exercise training can impact the sensitivity of this reflex, the molecular mechanisms that are at play remain unclear. Listen as Editor-in-Chief Irving H. Zucker interviews lead author Carlos Negrao (University of Sao Paulo) and expert Vaughan Macefield (University of Western Sydney) about the exciting new work by Antunes-Correa et al., who found that exercise training in chronic heart failure patients decreased the muscle mechanoreflex control of sympathetic nerve activity. Did Negrao and colleagues find that molecular abnormalities in skeletal muscle underlie abnormal muscle sympathetic nerve activity in humans with heart failure? Are these effects reversible with exercise training? Listen and learn more.

Ligia M. Antunes-Correa, Thais S. Nobre, Raphaela V. Groehs, Maria-Janieire N.N. Alves, Tiago Fernandes, Gisele K. Couto, Maria Urbana P.B. Rondon, Patricia Alves de Oliveira, Marta Lima, Wilson Mathias Jr., Patricia C. Brum, Charles Mady, Dirceu R. Almeida, Luciana Venturini Rossoni, Edilamar Menezes de Oliveira, Holly R. Middlekauff, Carlos Eduardo Negrao Molecular Basis for the Improvement in Muscle Metaboreflex and Mechanoreflex Control in Exercise-Trained Humans with Chronic Heart Failure Am J Physiol Heart Circ Physiol, published December 1, 2014. DOI: 10.1152/ajpheart.00136.2014.

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