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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CaMKII-Dependent Regulation of Atrial Late Sodium Current and Excitability

What is the interplay between late sodium current and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the early stages of atrial fibrillation induced by abnormal focal activity? Listen as Consulting Editor Igor Efimov (George Washington University) interviews lead author Thomas Hund (The Ohio State University) and content expert Patrick Boyle (Johns Hopkins University) about the unique modeling study by Onal et al. Hund and co-authors created a model focused on the CaMKII signaling pathway, itself dramatically altered in patients with atrial fibrillation, to piece together the sequence of events and mechanisms which trigger atrial arrhythmias. Hund and collaborators became interested in how CaM kinase II regulates the voltage-gated sodium channel, and their model allows for the cell to respond to various stimuli. Listen as our experts discuss how cell models portend the future of tissue-scale modeling (including a reference to the movie Jaws) and the necessity of balancing layers of complexity with the need for simplicity to maintain the integrity of the model.

 

Birce Onal, Daniel Gratz, Thomas J Hund Ca2+/calmodulin kinase II-dependent regulation of atrial myocyte late Na+ current, Ca2+ cycling and excitability: a mathematical modeling study Am J Physiol Heart Circ Physiol, published August 25, 2017. DOI: 10.1152/ajpheart.00185.2017

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Acylcarnitines in Human Heart Failure

What role do circulating acylcarnitines play in the heart failure metabolome? Listen as Guest Editor Sumanth Prabhu (University of Alabama at Birmingham) interviews lead author and Associate Editor Christine Des Rosiers (Universite de Montreal, Montreal Heart Institute), first author Matthieu Ruiz (Universite de Montreal, Montreal Heart Institute), and renowned content expert Heinrich Taegtmeyer (University of Texas Medical School), about the intriguing new study analyzing fatty acid metabolic perturbations in patients with heart failure with reduced ejection fraction (HFrEF). Des Rosiers and co-authors began their investigations over 10 years ago, and through persistence and new mass spectrometry analytical technologies, pursued a novel mechanism “contributing to the global lipid perturbation in human heart failure.” The work by Ruiz et al was published in the AJP-Heart and Circ Call for Papers on Heart Failure: Novel Therapeutic Pathways Emerging from Basic Science. This special extended podcast discusses the innovative techniques utilized by Des Rosiers, Ruiz and colleagues, along with the passion and tenacity required to understand the alterations in heart failure in long-chain fatty acid metabolism in heterogenous HFrEF patient cohorts. Did the authors find correlations to cardiac structural parameters, along with links between very long chain acylcarnitines and arrhythmias? Listen and learn.

 

Matthieu Ruiz, Francois Labarthe, Annik Fortier, Bertrand Bouchard, Julie Thompson Legault, Virginie Bolduc, Odile Rigal, Jane Chen, Anique Ducharme, Peter A Crawford, Jean-Claude Tardif, Christine Des Rosiers Circulating Acylcarnitine Profile in Human Heart Failure: A Surrogate of Fatty Acid Metabolic Dysregulation in Mitochondria and Beyond Am J Physiol Heart Circ Physiol, published July 14, 2017. DOI: 10.1152/ajpheart.00820.2016

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Cardio-postural Blood Pressure Control

How do the cardiac baroreflex and muscle pump systems work together to maintain blood pressure when you are standing? Listen as Associate Editor Robert Hester interviews authors Kouhyar Tavakolian (University of North Dakota) and Andrew Blaber (Simon Fraser University), along with content expert Jerry Collins (Alabama A & M University) about the innovative study by Xu et al. The authors explored the direct neural component between the brain and the muscle pump to help maintain blood pressure during a sit-to-stand transition, as well as a simple standing posture. Employing state-of-the-art analytics such as the wavelet transform coherence method and the convergent cross-mapping method, the authors simultaneously monitored the interrelationships between the human subjects’ cardiovascular, musculoskeletal, and balance systems. While the current study investigated young, healthy subjects, are there future implications for helping stroke patients, the elderly, or concussion injury patients? Listen and learn more.

 

Da Xu, Ajay Verma, Amanmeet Garg, Michelle Bruner, Reza Fazel-Rezai, Andrew P. Blaber, Kouhyar Tavakolian Significant role of the cardio-postural interaction in blood pressure regulation during standing Am J Physiol Heart Circ Physiol, published September 5, 2017. DOI: 10.1152/ajpheart.00836.2016

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Folic Acid and Exercise Hyperemia in Aging

What are the effects of folic acid on exercise-induced increases in blood flow in healthy older adults? Listen as Associate Editor Nancy Kanagy (University of New Mexico School of Medicine) interviews first author Steven Romero (UT Southwestern Medical Center) and content expert Thomas Barstow (Kansas State University) about the clinical translational study by Romero and co-authors investigating the role of folic acid in mitigating some of the profound changes in arterial vasculature and malperfusion of active skeletal muscle with aging. This innovative study is part of the AJP-Heart and Circulatory Physiology Call for Papers on Mining Natural Products for Cardiovascular Benefits. Is folic acid as a dietary supplement beneficial in preserving exercise capacity in older adults? This may bring new meaning to the adage “eat your spinach,” if doing so ameliorates the loss of nitric oxide in aging. Listen and learn more.

 

Steven A. Romero, Daniel Gagnon, Amy N Adams, Gilbert Moralez, Ken Kouda, Manall F Jaffery, Matthew N. Cramer, Craig G. Crandall Folic Acid Ingestion Improves Skeletal Muscle Blood Flow during Graded Handgrip and Plantar Flexion Exercise in Aged Humans Am J Physiol Heart Circ Physiol, published June 30, 2017. DOI: 10.1152/ajpheart.00234.2017

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Hypoxia Inducible Factor-alpha and Cancer Cachexia

How does cancer cachexia directly affect the heart? Listen as Deputy Editor Merry Lindsey (University of Mississippi Medical Center) tackles this question and more as she interviews lead author Loren Wold (The Ohio State University) and content expert Hemal Patel (VA San Diego Healthcare System, University of California San Diego) about the insightful study by Devine et al on cancer-induced cachexia and its effects on cardiac muscle structure and physiology. Using a proteomics approach, Wold and colleagues investigated how hypoxia inducible factor-1alpha served as a sensor for oxygen handling in the heart during cancer cachexia, a global hypoxic event. What strain and sex -dependent effects of tumor formation did Wold and co-authors observe in their model of cancer cachexia? Why was it significant that c-kit was elevated in the left ventricle of the tumor-bearing mice? Does lipid accumulation in the cachexia model bear resemblance to accelerated aging? Many questions, many answers. Listen now.

 

Raymond D. Devine, Sabahattin Bicer, Peter J. Reiser, Loren E. Wold Increased hypoxia-inducible factor-1α in striated muscle of tumor-bearing mice Am J Physiol Heart Circ Physiol, published June 1, 2017. DOI: 10.1152/ajpheart.00090.2016

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nNOS and Coronary Flow During Mental Stress

What is the mechanism by which mental stress affects cardiac performance? Listen as Associate Editor Fabio Recchia (Temple University Lewis Katz School of Medicine, and Scuola Superiore Sant'Anna, Pisa, Italy) interviews lead author, and fellow Associate Editor, Ajay Shah (King’s College London) along with content expert Nazareno Paolocci (Johns Hopkins University) about the clinical translational work by Khan et al. Shah and co-authors explored for the first time the effects of mental stress elicited by the Stroop color-word test and coronary flow and diameter on patients undergoing elective diagnostic coronary catheterization. The key finding is that neuronal nitric oxide synthase (nNOS), in additional to endothelial nitric oxide synthase (eNOS), contributes to the local regulation of coronary flow in response to mental stress. The authors showed that the Stroop test stimulated nNOS without altering heart rate and blood pressure. Does this indicate specific stimulation of the perivascular nerves? Listen now to this intriguing podcast exploring cross-talk between the brain and heart.

 

Sitara Gulurkh Khan, Narbeh Melikian, Husain Shabeeh, Ana Rita Cabaco, Katherine Martin, Faisal Khan, Kevin O'Gallagher, Phil Chowienczyk, Ajay M. Shah The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase Am J Physiol Heart Circ Physiol, published June 23, 2017. DOI: 10.1152/ajpheart.00745.2016

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