Diastolic Dysfunction in the Hypertensive mRen2 Rat

Do basic scientists now have a good animal model of heart failure with preserved ejection fraction (HFpEF) that mimics the human pathology? It’s very likely, according to the recent work by Kovacs et al. In this podcast, Editor in Chief Irving H. Zucker interviews lead author Arpad Kovacs (University of Debrecen, Hungary) and content expert Nazha Hamdani (VU University Medical Center, Amsterdam, and Ruhr University, Germany) about the fascinating new work by Kovacs and co-authors which seeks to understand the interplay between the renin-angiotensin-aldosterone system (RAAS) and hypertension in the unique mRen2 rat model of HFpEF. What role do the titin filament network and collagen fibers of the extracellular matrix play in LV diastolic dysfunction? Do the mechanisms underlying diastolic dysfunction hold the key to understanding if the hypertension associated with mRen2 rats is unique to this model or an inevitable consequence of hypertension? Listen now.

Árpád Kovács, Gabor Aron Fulop, Andrea Kovacs, Tamas Csipo, Beata Bodi, Daniel Priksz, Bela Juhasz, Lívia Beke, Zoltán Hendrik, Gábor Méhes, Henk Granzier, Istvan Edes, Miklós Fagyas, Zoltán Papp, Judit Barta, Attila Tóth Renin overexpression leads to increased titin-based stiffness contributing to diastolic dysfunction in hypertensive mRen2 rats Am J Physiol Heart Circ Physiol, published April 8, 2016. DOI: 10.1152/ajpheart.00842.2015


Dilated Cardiomyopathy Delta Sarcoglycan Mutations Cause Cardiomyocyte Membrane Instability

What is the link between mutations in delta sarcoglycans and dilated cardiomyopathy? In our latest podcast, Guest Editor Noah Weisleder (Ohio State University) interviews lead author Daniel Michele (University of Michigan) and content expert Aaron Beedle (University of Georgia) about this very question, digging deeper into the elegant study by Campbell et al which reveals that two different delta sarcoglycan mutations indeed have a dominant negative effect on myocyte membrane mechanical stability. Using a variety of experimental approaches—cellular, biochemical and functional assays—Dr. Michele and co-authors help to uncover the relationship between these genetic mutations and the presentation of the dilated cardiomyopathy phenotype. Learn more about how a personal connection to muscular dystrophy acted as a springboard for this study, part of our Call for Papers on Plasma Membrane Integrity in Cardiovascular Physiology and Pathophysiology. How do delta sarcoglycans guard against sarcolemma instability, and how does membrane repair differ from membrane integrity in dilated cardiomyopathy? Listen and find out.

Matthew D. Campbell, Marc Witcher, Anoop Gopal, Daniel E. Michele Dilated cardiomyopathy mutations in δ-sarcoglycan exert a dominant-negative effect on cardiac myocyte mechanical stability Am J Physiol Heart Circ Physiol, published May 1, 2016. DOI: 10.1152/ajpheart.00521.2015


Aging Impairs Endothelial Ca2+ Signaling

We know that as we age, blood vessels become less effective at getting blood where you need it, when you need it. Intracellular calcium signaling is a key step in regulation of vascular function. Could defects in calcium signaling between the endothelium and smooth muscle cells of microvessels contribute to aging-related vascular dysfunction? Listen as Guest Editor Akos Koller (New York Medical College, Valhalla, and University of Physical Education, Budapest) interviews first author Erika Boerman (University of Missouri - Columbia) and topic expert Jonathan Ledoux (Montreal Heart Institute) about an innovative Rapid Report by Boerman and colleagues. Using an intravital microvascular preparation, Boerman et al combined several innovative techniques from other laboratories, including GCamp 2 mice developed as a calcium biosensor for measuring calcium pulsars, to explore calcium signaling in holes within the internal elastic lamina between the endothelium and smooth muscle. If the number of these holes reduces with aging, is there a corresponding decreased capacity for myoendothelial calcium signaling, which then can contribute to age-related microvascular dysfunction? Listen and learn.

Erika M. Boerman, Jesse E. Everhart, Steven S. Segal Advanced age decreases local calcium signaling in endothelium of mouse mesenteric arteries in vivo Am J Physiol Heart Circ Physiol, published May 1, 2016. DOI: 10.1152/ajpheart.00038.2016.