Dantrolene suppresses Ca2+ sparks and Ca2+ waves

In this podcast we highlight the recent study by Domeier and colleagues, which looked for a way to pharmacologically restore proper function of the ryanodine receptor with advancing age. Did they find it? Editor in Chief Dr. Irving Zucker interviews lead author Timothy Domeier (The University of Missouri School of Medicine) and expert Eric Sobie (Mount Sinai School of Medicine) about this fascinating study investigating whether ryanodine receptor mediated calcium release in the aged heart was altered by dantrolene. In fact, Domeier and colleagues did find that dantrolene provided a protective effect against pro-arrhythmic calcium sparks and calcium waves in diastole. Hear about this finding and much more by clicking play below.

Timothy L. Domeier, Cale J. Roberts, Anne K. Gibson, Laurin M. Hanft, Kerry S. McDonald, Steven S. Segal Dantrolene suppresses spontaneous Ca2+ release without altering excitation-contraction coupling in cardiomyocytes of aged mice Am J Physiol Heart Circ Physiol, published September 15, 2014. DOI: 10.1152/ajpheart.00287.2014.

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Noninvasive Longitudinal Measurements of [Ca2+] in Arterioles of Hypertensive Optical Biosensor Mice

Have noninvasive calcium signaling measurement methods turned a new corner? Yes, according to a unique new study by Mauban et al. Associate Editor Nancy Kanagy interviews senior author W. Gil Wier (University of Maryland School of Medicine) and leading expert Mark Nelson (University of Vermont) about the work by Wier and colleagues, which measured intracellular levels of calcium noninvasively in the same animal over a period of several weeks. How? Wier and co-authors ingeniously immobilized the mouse ear, enabling the use of a FRET-based ratiometric calculation of actual intracellular calcium levels in vascular cells inside the living animal. Does this innovative methodology launch new possibilities for evaluating calcium signaling changes during disease development? Listen and find out.

Joseph R. H. Mauban, Seth T. Fairfax, Mark A. Rizzo, Jin Zhang, Withrow Gil Wier A method for noninvasive longitudinal measurements of [Ca2+] in arterioles of hypertensive optical biosensor mice Am J Physiol Heart Circ Physiol, published July 15, 2014. DOI: 10.1152/ajpheart.00182.2014.

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DDR2 Deletion in the Heart

What happens to the left ventricle and cardiac fibroblasts when DDR2 (Discoidin Domain Receptor 2) is deleted? Deputy Editor Merry Lindsey interviews lead author Randy Cowling (University of California San Diego) and expert Angelo Calderone (Montreal Heart Institute/Universite de Montreal) about the novel work by Cowling and colleagues, which explored the surprising finding that DDR2 deletion resulted in less densely packed collagen that altered myocyte contractility. Does this work provide a stepping stone to deeper investigation of the intricacies of collagen deposition by cardiac fibroblasts? Given the “plasticity” of fibroblast phenotypes, what are the implications of pathological stimuli— for example, post-myocardial infarction? Listen and learn more.

Randy T Cowling, Seon Ju Yeo, In Jai Kim, Joong Il Park, Yusu Gu, Nancy D. Dalton, Kirk L. Peterson, Barry H Greenberg Discoidin Domain Receptor 2 (DDR2) Germline Gene Deletion Leads to Altered Heart Structure and Function in the Mouse Am J Physiol Heart Circ Physiol, published online July 3, 2014. DOI: 10.1152/ajpheart.00142.2014.

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TIMP-4 and Left Ventricular Pressure Overload

How does TIMP-4 really behave in the myocardium, and what is its role in the pressure overload response to transverse aortic constriction? In this engaging author interview, Deputy Editor Merry Lindsey talks with lead author Francis Spinale (University of South Carolina School of Medicine and WJB Dorn VA Medical Center) and expert Zamaneh Kassiri (University of Alberta) about the work by Yarbrough et al, which surprisingly showed that inducing TIMP-4 in the setting of pressure overload may be beneficial. Have Spinale and colleagues opened the door to a sea-change in the current canonical thinking of TIMP roles? Listen and find out.

William M. Yarbrough, Catalin F. Baicu, Rupak Mukherjee, An O. Van Laer, William T. Rivers, Richard A. McKinney, Corey B. Prescott, Robert E. Stroud, Parker D. Freels, Kia N. Zellars, Michael R. Zile, Francis G. Spinale Cardiac Restricted Overexpression Or Deletion Of Tissue Inhibitor Of Matrix Metalloproteinase-4 Am J Physiol Heart Circ Physiol, published online July 3, 2014. DOI: 10.1152/ajpheart.00063.2014.

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Deformation Causes Vascular Alignment During Angiogenesis

What does “changing the boundary conditions” mean? In our latest author interview, Deputy Editor Dr. Merry Lindsey asks lead author Dr. Jeffrey Weiss (University of Utah) this very question about his innovative new work exploring the relationship between tissue mechanics and angiogenesis. Expert Hai-Chao Han (University of Texas at San Antonio) lends his insight into the importance of studying the mechanics of blood vessel formation. Will the work by Underwood et al, which elegantly blends computational and biological approaches, someday lead to new experimental applications, such as pre-aligned microvasculatures for engineered tissue constructs? Listen and learn.

Clayton J. Underwood, Lowell T. Edgar, James B. Hoying, Jeffrey A. Weiss Cell-generated traction forces and the resulting matrix deformation modulate microvascular alignment and growth during angiogenesis Am J Physiol Heart Circ Physiol, published July 15, 2014. DOI: 10.1152/ajpheart.00995.2013.

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Wave Potential and the One-Dimensional Windkessel

While wave separation analysis is considered the gold standard for assessing pressure and flow waves in the arterial system, how do we account for self-cancelling flow waves during diastole? In this podcast Associate Editor Dr. Masafumi Kitakaze interviews lead author Jonathan Mynard (Murdoch Children’s Research Institute, Australia) and expert Berend Westerhof (Edwards Lifesciences BMEYE, Netherlands) about the innovative work by Mynard and co-author Joseph Smolich, which used mathematical models and experimental studies in sheep to discover the novel concepts of wave potential and the one-dimensional windkessel. With attention now being paid to the origin and behavior of self-cancelling diastolic waves, we may be poised to better understand the relationship between pressure and flow in cardiovascular health and disease states. Listen now and learn more.

Jonathan P Mynard , Joseph J. Smolich Wave potential and the one-dimensional windkessel as a wave-based paradigm of diastolic arterial hemodynamics Am J Physiol Heart Circ Physiol, published May 30, 2014. DOI: 10.1152/ajpheart.00293.2014.

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Aromatase Modulates Cardiac Ischemic Stress Response

Beyond vascular effects, can estrogen produced in the heart have an influence on cardiac function? Is the local action of aromatase conversion of testosterone to estrogen important for the stressed heart? Listen as Guest Editor Dr. Virginia Miller interviews lead author Lea Delbridge (University of Melbourne) and expert Fred Naftolin (New York University) about the exciting new work by Bell et al showing aromatase expression in the heart at both the messenger and protein level. Given that the human heart is sexually dimorphic, and that this may extend past development to actual function, what insightful differences did the authors find in male and female aromatase transgenic mouse hearts? Listen now.

James R. Bell, Gabriel B. Bernasochi, Upasna Varma, Wah Chin Boon, Stuart J. Ellem, Gail P. Risbridger, Lea M. D. Delbridge Aromatase transgenic upregulation modulates basal cardiac performance and the response to ischemic stress in male mice Am J Physiol Heart Circ Physiol, published May 1, 2014. DOI: 10.1152/ajpheart.00012.2014.

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Aortic Valve Sclerosis in Mice Deficient in Endothelial Nitric Oxide Synthase

What is the sequence of events in the formation of fibrosis and calcification in aortic valves, and what role does endothelium-derived nitric oxide play in these pathways? Listen as Associate Editor Ajay Shah interviews lead author Robert Weiss (University of Iowa) and expert Jane Leopold (Brigham and Women's Hospital) about the innovative and novel work by El Accaoui et al. With a unique combination of in vitro co-culture and in vivo knockout mouse studies, Weiss and colleagues seek to shed light on a clinically-relevant and increasingly important question: when does aortic sclerosis begin and how can it be treated before aortic stenosis develops?

Ramzi N. El Accaoui, Sarah T. Gould, Georges P. Hajj, Yi Chu, Melissa K. Davis, Diane C. Kraft, Donald D. Lund, Robert M. Brooks, Hardik Doshi, Kathy A. Zimmerman, William Kutschke, Kristi S. Anseth, Donald D. Heistad, Robert M. Weiss Aortic valve sclerosis in mice deficient in endothelial nitric oxide synthase Am J Physiol Heart Circ Physiol, published May 1, 2014. DOI: 10.1152/ajpheart.00392.2013.

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The Role of EETs in Pressure-induced Vasoconstriction

What’s new in skeletal muscle arteries? Research by Sun et al demonstrates, for the first time, metabolic regulation of myogenic tone in a skeletal muscle small resistance artery by EETs. Listen as Associate Editor Mordy Blaustein interviews lead author An Huang (New York Medical College) and expert David Harder (Medical College of Wisconsin) about this innovative knock-out mouse model, responses of different types of vascular beds to various vasodilatory agents, and the importance of basic studies on SEH inhibitors as the backbone of clinical trials.

Dong Sun, Azita J. Cuevas, Katherine Gotlinger, Sung Hee Hwang, Bruce D. Hammock, Michal L. Schwartzman, An Huang Soluble epoxide hydrolase-dependent regulation of myogenic response and blood pressure Am J Physiol Heart Circ Physiol, published April 15, 2014. DOI: 10.1152/ajpheart.00920.2013.

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Paternal Low Protein Diet and Adult Offspring Health in Mice

Should we change the old adage “you are what you eat” instead to “you are what your parents eat”? A new study by Adam Watkins and Kevin Sinclair investigates the correlation between a low protein paternal diet and the X and Y bearing sperm. While we have long understood the effects of maternal nutrition during pregnancy on offspring cardiovascular and metabolic health, does the same hold true for the paternal side of the equation during conception? Listen as Consulting Editor Steven P. Jones interviews lead author Adam Watkins (Aston University, United Kingdom) and expert Christopher Torrens (University of Southampton, United Kingdom) about this integrative cardiovascular physiology work that seeks to understand: Could what a male eats determine the gender of his offspring?

Adam J. Watkins , Kevin D. Sinclair Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice Am J Physiol Heart Circ Physiol, published May 15, 2014. DOI: 10.1152/ajpheart.00981.2013.

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