mTOR Prevents Ferroptosis in Cardiomyocytes

What differentiates ferroptosis in the heart from apoptosis and necrosis? Listen as Deputy Editor Merry Lindsey (University of Mississippi Medical Center) interviews lead author Takashi Matsui (University of Hawai'i) and content expert Lorrie Kirshenbaum (St. Boniface General Hospital Research Centre, Canada) about the exciting new study by Baba et al, one of the first to show that ferroptosis is distinct from autophagy, apoptosis and necrosis in cardiomyocytes. Ferroptosis is cell death characterized by excessive levels of iron and to iron-mediated reactive oxygen species generation. Did the authors find that glutathione peroxidase 4 (GPX4) played a role in cardiomyocyte ferroptosis? What connection did the authors find between the mTor pathway and iron-mediated cell death in cardiomyocytes? Listen, read, and view the beautiful cardiomyocyte isolation images to learn more.

 

Yuichi Baba, Jason K Higa, Briana K Shimada, Kate M. Horiuchi, Tomohiro Suhara, Motoi Kobayashi, Jonathan D. Woo, Hiroko Aoyagi, Karra S Marh, Hiroaki Kitaoka, and Takashi Matsui Protective Effects of the Mechanistic Target of Rapamycin against Excess Iron and Ferroptosis in Cardiomyocytes Am J Physiol Heart Circ Physiol, published November 10, 2017. DOI: 10.1152/ajpheart.00452.2017

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Guidelines on Antibody Use in Physiology Studies

It is nearly impossible to avoid using antibodies in biological research, but are cardiovascular researchers validating reagents the right way? In our latest podcast on Guidelines in Cardiovascular Research, Editor in Chief Irving H. Zucker (University of Nebraska Medical Center) interviews authors Heddwen L. Brooks (University of Arizona) and Deputy Editor Merry L. Lindsey (University of Mississippi Medical Center), along with expert John Hollander (West Virginia University School of Medicine) about how best to advise researchers on antibody use in immunohistochemistry and immunoblotting for evaluating expression of specific proteins in the cells and tissues of interest. Given the ongoing call for increased rigor and reproducibility in scientific research, this Guidelines article podcast offers investigators a roadmap to what controls should be performed and what information should be recorded when using antibodies in cardiovascular physiology research. Listen now.

 

Heddwen L Brooks and Merry L. Lindsey Guidelines for Authors and Reviewers on Antibody Use in Physiology Studies Am J Physiol Heart Circ Physiol, published January 5, 2018. DOI: 10.1152/ajpheart.00512.2017

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Endothelial Control of Blood Pressure

Do changes in endothelial function in a high-fat, high-sugar diet model of metabolic syndrome mitigate the effects of elevated sympathetic nervous system activity to increase blood pressure? Listen as Associate Editor Debra Diz (Wake Forest University School of Medicine) interviews first author Sylvain Battault (Avignon University, France) and content expert Julie Y.H. Chan (Chung Gung Memorial Hospital, Taiwan) about the intriguing new work by Battault and co-authors which has potential clinical implications for obesity with, and without, hypertension. Did the authors find that an increase in autonomic sympathetic outflow translates to high blood pressure in their model of metabolic syndrome? Does this study suggest that the endothelium modulates adrenergic-dependent vasoconstriction as a last-chance defense mechanism against metabolic syndrome -associated hypertension? Listen and find out.

 

Sylvain Battault, Cindy Meziat, Alessandro R Nascimento, Laura Braud, Sandrine Gayrard, Christian Legros, Frederic De Nardi, Jocelyne Drai, Olivier Cazorla, Jérôme Thireau, Gregory Meyer, and Cyril Reboul Vascular endothelial function masks increased sympathetic vasopressor activity in rats with metabolic syndrome Am J Physiol Heart Circ Physiol, published November 10, 2017. DOI: doi/10.1152/ajpheart.00217.2017

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NRG-1 Inhibits Macrophage Activation During Tissue Fibrosis

Does neuregulin-1 (NRG-1) directly affect macrophages present during the inflammatory phase of cardiac fibrosis? Listen as Deputy Editor Merry Lindsey (University of Mississippi Medical Center) interviews authors Gilles De Keulenaer and Vincent Segers (both at University of Antwerp, Belgium) and content expert Amy Bradshaw (Medical University of South Carolina) about the novel study by Vermeulen et al. What “accidental discovery” in the lab lead the authors to expand their study of NRG-1 in the fibrosis of the heart to skin and lung? Are the similarities in collagen deposition in the extracellular matrix of the heart, skin, lung and other tissues driven by macrophages? “Paying attention to accidental discoveries can lead to new avenues of research,” said Dr. Merry Lindsey. Did the authors find that the neuregulin-ErbB4 system plays a role in both interstitial and perivascular fibrosis? Listen and find out.

 

Zarha Vermeulen, Anne-Sophie Hervent, Lindsey Dugaucquier, Leni Vandekerckhove, Miche Rombouts, Matthias Beyens, Dorien M. Schrijvers, Guido R. Y. De Meyer, Stuart Maudsley, Gilles W. De Keulenaer*, and Vincent F. M. Segers Inhibitory actions of the NRG-1/ErbB4 pathway in macrophages during tissue fibrosis in the heart, skin, and lung Am J Physiol Heart Circ Physiol, published November 1, 2017. DOI: 10.1152/ajpheart.00206.2017

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Chinese - English Language Podcast on Differential Cardiac Remodeling in TAC vs AR

Special Dual Language Podcast in Chinese and English: What fascinating findings are presented on the differences between pressure overload and volume overload induced cardiac hypertrophy? Listen to this intriguing podcast as Professor Jie Liu from Shenzhen University of China interviews the corresponding authors Drs. Yunzeng Zou and Jian Wu from Fudan University of China, and the first author Dr Jieyun You from Tongji University, talking about their work on different phenotypic, functional and molecular adaptations in cardiac hypertrophy under different mechanical stress. The authors utilized a mouse model of pressure overload induced by transverse aortic constriction, and a newly developed mouse model of volume overload induced by aortic regurgitation, to make a comparative study on the differences between the two types of cardiac hypertrophy. What are the prominent differences between the two types of hypertrophy? Which hypertrophy seems more benign? What are the translational implications for personalized therapeutics for cardiac hypertrophy? Listen now and learn more. 

 

Jieyun You, Jian Wu, Qi Zhang, Yong Ye, Shijun Wang, Jiayuan Huang, Haibo Liu, Xiaoyan Wang, Weijing Zhang, Liping Bu, Jiming Li, Li Lin, Junbo Ge, and Yunzeng Zou Differential cardiac hypertrophy and signaling pathways in pressure versus volume overload Am J Physiol Heart Circ Physiol, published December 1, 2017. DOI: 10.1152/ajpheart.00212.2017

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Update on Hormone Therapy Trials

Did the publication of the Women’s Health Initiative (WHI) in 2002 lead to assumptions that may prevent menopausal women from being properly treated? Listen to this enlightening conversation as Editor in Chief Dr. Irving H. Zucker (University of Nebraska Medical Center) interviews senior author Virginia M. Miller (Mayo Clinic College of Medicine) and content expert Barbara Alexander (University of Mississippi) about the new review article by Miller and Harman aimed at understanding the controversies surrounding the WHI and menopausal hormone therapy. This engaging podcast provides a primer on the WHI, confronts the dangers of using imprecise terminology (conjugated equine estrogen compared to 17β-estradiol), and shines a light on the still-evolving study of menopausal hormone therapy. Do the limitations of the Women’s Health Initiative still have repercussions for the daily lives of menopausal women some 15 years post-publication? Listen now.

 

Virginia M. Miller and S. Mitchell Harman An update on hormone therapy in postmenopausal women: mini-review for the basic scientist  Am J Physiol Heart Circ Physiol, published November 1, 2017. DOI: 10.1152/ajpheart.00383.2017

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Aging, Exercise, and Endothelial Cell Senescence

Can regular aerobic exercise diminish the damaging effects of aging on the vascular system by improving the health of vascular endothelial cells? In this insightful podcast, Associate Editor Nancy Kanagy interviews lead author Matthew Rossman (University of Colorado Boulder) and content expert Raymond Migrino (Phoenix VA Health Care System) about the work by Rossman et al focusing on age-related changes in endothelial cell senescence and associated changes in endothelial cell function that occurs with normal, healthy aging. Habitual exercise has been shown to reduce age-related phenotypic changes such as increased arterial stiffness and reduced endothelial cell function. Did Rossman and colleagues find that regular aerobic exercise in older adults ameliorated increases in endothelial cell senescence? Listen and learn more.

 

Matthew J. Rossman, Rachelle E. Kaplon, Sierra D. Hill, Molly N. McNamara, Jessica R. Santos-Parker, Gary L. Pierce, Douglas R. Seals, Anthony J. Donato Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function Am J Physiol Heart Circ Physiol, published November 1, 2017. DOI: 10.1152/ajpheart.00416.2017

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Low Carb Diet and Exercise Improve Endothelial Health

Does the combination of a low carbohydrate meal and post-meal walking exercise help to avoid hyperglycemia, and improve vascular function, in Type 2 diabetes patients? In this podcast, Consulting Editor Nisha Charkoudian (United States Army Research Institute of Environmental Medicine) interviews first author Monique Francois (University of Virginia) and content expert Sushant Ranadive (University of Maryland) about the innovative study by Francois and co-authors. While it is well known that low carb diets lower blood glucose, often low carb diets are high in fat, which then impairs endothelial function. Did the authors find that by combining low carb meals with post-meal exercise, endothelial function was improved? How did endothelial microparticles respond to the low-carb diet vs. the low-carb plus post-meal walking protocol? Is it the timing of exercise that is the key factor to improve postprandial metabolism? Listen to learn more.

 

Monique Emily Francois, Etienne Myette-Cote, Tyler Daniel Bammert, Cody Durrer, Helena Neudorf, Christopher A. DeSouza, Jonathan Peter Little Carbohydrate-restriction with Postmeal Walking Effectively Mitigates Postprandial Hyperglycemia and Improves Endothelial Function in Type 2 Diabetes Am J Physiol Heart Circ Physiol, published October 136, 2017. DOI: 10.1152/ajpheart.00524.2017

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Treadmill BP in Simulated Peripheral Artery Disease

What is driving the exaggerated blood pressure response to exercise in patients with peripheral arterial disease (PAD)? In this podcast, Editor in Chief Irving H. Zucker (University of Nebraska Medical Center) interviews senior author Gail Thomas (Penn State College of Medicine) and content expert Hanjun Wang (University of Nebraska Medical Center) about the unique study by Kuczmarski et al. Thomas and co-authors used telemetry to record blood pressure during exercise in conscious animals, both before and after bi-lateral femoral artery ligation. The studied was conducted over a period of two months, a technical success given that the authors used chronically-instrumented conscious animals. Thomas and collaborators found that the blood pressure response was exaggerated as early as 3 days after femoral artery ligation and lasted for the duration of the experiment in both female and male mice. Are the mechanisms that play a role in blood pressure response to short-term ligation, such as cytokines IL-6 and activation of the purinergic P2X3 receptors, also at work here? Listen and find out.

 

J. Matthew Kuczmarski, Kellee Unrath, Gail D. Thomas Exaggerated cardiovascular responses to treadmill running in rats with peripheral arterial insufficiency Am J Physiol Heart Circ Physiol, published October 6, 2017. DOI: 10.1152/ajpheart.00401.2017

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Calcium Regulation in E99K Mouse Heart

What is the role of calcium transients in sudden cardiac death associated with hypertrophic cardiomyopathy? Listen as Associate Editor Gary Lopaschuk (University of Alberta) interviews lead author Steven Marston (Imperial College London) and content expert Susan Howlett (Dalhousie University) about the work by Marston and colleagues, who studied alterations in calcium handling in a unique transgenic mouse model of hypertrophic cardiomyopathy, a common form of cardiac hypertrophy. Analyzing both calcium waves and calcium sparks, Marston and co-authors found that the proportion of transgenic mice which had a higher spark mass did succumb to sudden cardiac death at 40 days old. In comparison, older transgenic mice and younger non-transgenic mice with a lower spark mass did not die of sudden cardiac death. Given that the transgenic mice showed spontaneous calcium release and more frequent calcium sparks, did the authors find these mice had a higher incidence of arrhythmias? Does the strain of mice used in the transgenic model have implications on study results? Listen to find out.

 

Christina Rowlands, Thomas Owen, Saheed Lawal, Shuangyi Cao, Samata Pandey, Hsiang-Yu Yang, Weihua Song, Ross Wilkinson, Anita Alvarez-Laviada, Katja Gehmlich, Steven Marston, Kenneth T. MacLeod Circulating Age and strain related aberrant Ca2+ release is associated with sudden cardiac death in the ACTC E99K mouse model of hypertrophic cardiomyopathy Am J Physiol Heart Circ Physiol, published September 8, 2017. DOI: 10.1152/ajpheart.00244.2017

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