Metabolic Syndrome and Cerebral Vascular Function

Riddle me this: if you were going to be stuck on an island with only one drug, which drug offers “the best bang for your buck” in controlling metabolic syndrome due to obesity? That’s just one question we tackle in this podcast about the translational work by Brooks et al on how metabolic syndrome in obesity affects the cerebral microvasculature, published as part of our Call for Papers on Small Vessels – Big Problems. Guest Editor Akos Koller (New York Medical College and University of Physical Education, Budapest, Hungary) interviews lead author Paul Chantler (West Virginia University) and content expert Julian Lombard (Medical College of Wisconsin) about the adaptions in cerebral circulation during the progression of metabolic syndrome using an obese Zucker rat model of human disease. How do pharmacological interventions aimed at treating major risk factors such as blood pressure and glucose levels affect cerebrovascular changes in metabolic syndrome? With metabolic syndrome affecting nearly 57 million adults in the U.S., you can’t afford not to listen to this engaging, insightful podcast.


Steven D. Brooks, Evan DeVallance, Alexandre C. d'Audiffret, Stephanie J. Frisbee, Lawrence E. Tabone, Carl D. Shrader, Jefferson C. Frisbee, Paul D. Chantler Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats Am J Physiol Heart Circ Physiol, published December 1, 2015, DOI: 10.1152/ajpheart.00691.2015.

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Determinants of Intra-cardiac Kinetic Energy

What do we know about the kinetic energy of intra-cardiac blood flow during the two phases of the cardiac cycle? Virtually nothing. That’s what Steding-Ehrenborg et al seek to change in a new study we explore in this podcast. Listen as Associate Editor Fabio Recchia (Temple University Lewis Katz School of Medicine, and Scuola Superiore Sant'Anna, Pisa, Italy) interviews lead author Katarina Steding-Ehrenborg (Lund University) and content expert Martin Ugander (Karolinska University Hospital) about how the authors used state-of-the-art cardiac magnetic resonance imaging with 4-dimensional phase-contrast sequences to compare kinetic energy in atrial and ventricular chambers in both healthy volunteers and elite endurance athletes. What are the differences in the filling mechanisms between the two chambers of the heart, and how does this affect cardiac pump function? What does high, or low, intra-cardiac blood flow kinetic energy really mean? Listen as we unpack the details of this intriguing, ground-breaking new work.


Katarina Steding-Ehrenborg, Per Martin Arvidsson, Johannes Toger, Mattias Rydberg, Einar Heiberg, Marcus Carlsson, Hakan Arheden Determinants of kinetic energy of blood flow in the four-chambered heart in athletes and sedentary controls Am J Physiol Heart Circ Physiol, published January 1, 2016. DOI: 10.1152/ajpheart.00544.2015.

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Roles of CSE and MPST in Coronary Vasoregulation

What role does hydrogen sulfide play in coronary vascular function? That’s just what lead author Lakshmi Santhanam and colleagues set out to uncover in the work by Kuo et al, which we discuss in this podcast. Associate Editor Nancy Kanagy (University of New Mexico School of Medicine) interviews Santhanam (Johns Hopkins University) and content expert Christopher Kevil (Louisiana State University) about the role and source of hydrogen sulfide in coronary arteries and the discovery that the endothelial enzyme 3-mercaptypyruvate sulfertransferase (MPST) is the primary regulator. Does MPST operate in other vascular beds? Are the fluorescence indicators used by Santhanam and co-authors a reliable tool to detect real-time measurements of hydrogen sulfide production? Listen and find out.


Maggie M. Kuo, Dae Hee Kim, Sandeep Jandu, Yehudit Bergman, Siqi Tan, Huilei Wang, Deepesh R. Pandey, Theodore P. Abraham, Artin A. Shoukas, Dan E. Berkowitz, Lakshmi Santhanam MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery Am J Physiol Heart Circ Physiol, published January 1, 2016. DOI: 10.1152/ajpheart.00574.2014.

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Radiation-Induced Regulatory Networks in Cardiomyocytes

What do deep space travel and AJP-Heart and Circ have in common? This podcast. Listen as Associate Editor Leon De Windt interviews lead author David Goukassian (Boston University School of Medicine) and content expert Martin E. Young (University of Alabama at Birmingham) about the intriguing new study by Coleman et al. Goukassian and his team studied the effects of low dose, full body, low energy radiation on heart physiology. This type of radiation is relevant for radiotherapy and for future deep space travel by astronauts when mankind starts exploring our galaxy. At a dose of 0.15 Grey iron particles, cardiomyocytes demonstrated long-lived changes in gene expression consistent with inflammatory and free radical scavenging gene ontologies. We discussed how space travel could disrupt our circadian rhythm, our natural 24 hour day/night cycle. In addition, this study give clues as to which regions of deep space we should avoid in order to protect our circadian rhythm. Finally, we speculated about the existence of radiation-specific diagnostic markers, and how anti-inflammatory agents may be used in the future for treatment of radiation-induced tissue damage. Listen-- it is fascinating.


Matthew A. Coleman, Sharath P. Sasi, Jillian Onufrak, Mohan Natarajan, Krishnan Manickam, John Schwab, Sujatha Muralidharan, Leif E. Peterson, Yuriy O. Alekseyev, Xinhua Yan, David A. Goukassian Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes Am J Physiol Heart Circ Physiol, published December 1, 2015, DOI: 10.1152/ajpheart.00050.2015.

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Calpastatin Overexpression Impairs Post-MI Scar Healing

Timing is everything, and so it was with calpastatin overexpression used to inhibit calpain activity and impair post-MI scar formation. In this podcast, Deputy Editor Merry Lindsey (University of Mississippi Medical Center) interviews lead author Barnabas Gellen (CHU de Poitiers) and content expert Gerd Heusch (Universitatsklinikum Essen) in an engaging discussion about the recent work by Wan et al. This study, which evolved from an initially planned long-term experiment to focus on short-term remodeling effects, is a great example of results refining evaluation parameters. In terms of experimental design strategy, find out how permanent coronary occlusion compares to ischemia reperfusion. “Mechanism comes first, and then we can translate it,” said Heusch. “So, both models have their value.” The exciting results of this study lead Gellen and colleagues to ask: when should we start calpain inhibition, when should we stop calpain inhibition, how much inhibitory effect is beneficial, and in which cell types? Listen to find out.


Feng Wan, Emmanuel Letavernier, Claude Jourdan Le Saux, Amal Houssaini, Shariq Abid, Gabor Czibik, Daigo Sawaki, Elisabeth Marcos, Jean-Luc Dubois-Rande, Laurent Baud, Serge Adnot, Geneviève Derumeaux, Barnabas Gellen Calpastatin overexpression impairs postinfarct scar healing in mice by compromising reparative immune cell recruitment and activation Am J Physiol Heart Circ Physiol, published December 1, 2015. DOI: 10.1152/ajpheart.00594.2015.

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Mitochondrial Flash: Novel Biomarker of Mitochondrial Respiration

What are mitochondria flash events, and are the flash coupled to the flow of electrons along the electron transport chain during mitochondrial respiration? In this podcast Associate Editor Ronglih Liao (Brigham and Women's Hospital and Harvard Medical School) interviews lead author Wang Wang (University of Washington) and content expert Hossein Ardehali (Northwestern University) about the study by Gong et al, which goes beyond Wang’s pioneering discovery of mitochondria flash to imaging flash and measuring mitochondria respiration. Might the imaging techniques used by Wang and co-authors lead to analysis of mitochondrial respiration in tissues other than the heart, such as skeletal muscle? While mitochondria flash can be used to measure reactive oxygen species (ROS) production inside the cell, can this innovative technique, in combination with pharmacological approaches, pinpoint the exact source of ROS production? Listen to find out.


Guohua Gong, Xiaoyun Liu, Huiliang Zhang, Shey-Shing Sheu, Wang Wang Mitochondrial flash as a novel biomarker of mitochondrial respiration in the heart Am J Physiol Heart Circ Physiol, published October 1, 2015, DOI: 10.1152/ajpheart.00462.2015.

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Clock Dysfunction Triggers Fibrotic Response in the Heart

What is the role of the circadian clock component Bmal1 in cardiac function? Deputy Editor Merry Lindsey (University of Mississippi Medical Center) interviews lead author Ganesh Halade (University of Alabama at Birmingham) and expert Amanda Le Blanc (University of Louisville) in this engaging podcast about the work by the Young and Halade laboratories, which found a “striking” result: cardiomyocyte specific Bmal1 deletion not only triggered the development of diastolic dysfunction, adverse extracellular matrix remodeling, and inflammation, but also drastically reduced the lifespan of mice compared to control litter mates. Do the Ingle et al results indicate that cardiomyocytes are an early, upstream regulator of aging in the heart? Listen and learn.


Kevin A. Ingle, Vasundhara Kain, Mehak Goel, Sumanth D. Prabhu, Martin E. Young, Ganesh V Halade Cardiomyocyte specific Bmal1 deletion in mice triggers diastolic dysfunction, extracellular matrix response and impaired resolution of inflammation Am J Physiol Heart Circ Physiol, published online October 2, 2015, DOI: 10.1152/ajpheart.00608.2015.

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Heart Failure Alters Synaptic Input in Cardiac Vagal Neurons

Is a reduction in parasympathetic activity the “canary in the coal mine” at the onset of many cardiovascular diseases, such as hypertension and heart failure? Listen as Associate Editor Kaushik Patel (University of Nebraska Medical Center) interviews lead author David Mendelowitz (George Washington University) and content expert Helio Salgado (University of São Paulo) about why Cauley et al set out to understand what changes cardiac vagal activity at the level of the brainstem using an aortic constriction model of heart failure. While much is known about alterations in sympathetic nerve activity, the knowledge of parasympathetic activity is still in its infancy. Could leveraging the diverse populations of neurons within the paraventricular nucleus of the hypothalamus provide a mechanism to alter the sympathetic-parasympathetic balance? Would stimulating parasympathetic activity, either at the level of the ganglia or brainstem, provide cardioprotective benefits in cardiovascular diseases, such as hypertension and heart failure? Listen to find out.


Edmund Cauley, Xin Wang, Jhansi Dyavanapalli, Ke Sun, Kara Garrott, Sarah Kuzmiak-Glancy, Matthew W Kay, David Mendelowitz Neurotransmission to Parasympathetic Cardiac Vagal Neurons in the Brainstem is Altered With Left Ventricular Hypertrophy Induced Heart Failure Am J Physiol Heart Circ Physiol, published September 14, 2015, DOI: 10.1152/ajpheart.00445.2015.

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CLIC4 Regulates Maturation of Cerebral Collaterals

What are collateral arterioles, and how can the number of such collaterals in the brain affect recovery from stroke? Listen as Guest Editor Akos Koller (New York Medical College) interviews first author Jennifer Lucitti (University of North Carolina at Chapel Hill) and content expert Mordecai Blaustein (University of Maryland Medical School) about this fascinating new study, which investigated the formation of collaterals both pre- and postnatal, as well as the role of chloride intracellular channel 4 (CLIC4) protein in collateral formation. Lucitti and colleagues found that there is a specific time when collaterals formed during embryogenesis, which can be very important later in life if larger arteries are blocked. At the molecular level, what exciting relationship did the authors find between vascular endothelial growth factor-A (VEGF-A) and CLIC 4 during collaterogenesis? Is prevention of collateral pruning and enhancement of collateral stabilization later in life a promising therapeutic target for stroke? Listen now.


Jennifer L. Lucitti, Natalie J. Tarte, James E. Faber Chloride intracellular channel 4 is required for maturation of the cerebral collateral circulation Am J Physiol Heart Circ Physiol, published October 1, 2015, DOI: 10.1152/ajpheart.00451.2015.

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Cardioprotective Effects of Intrinsic STAT3 in Subacute MI

While STAT3 has been shown to protect the heart post myocardial infarction during cardiac remodeling, is persistent activation of the STAT3 gene protecting or hurting the heart? In the English version of this dual language podcast, Associate Editor Junichi Sadoshima (Rutgers New Jersey Medical School) interviews lead author Yasushi Fujio (Osaka University) and content expert Yasuko Bando (Nagoya University) about the innovative work by Enomoto et al, in which Fujio and his collaborators created cardiac-specific conditional STAT3 knockout mice designed to knockout STAT3 only after myocardial infarction. In STAT3 null mice, ROS production increased, which then lead to a cascade of negative effects, first inducing cardiac hypertrophy, then suppressing angiogenesis. Is suppression of superoxide production the primary cardioprotective pathway of STAT3? Listen to learn more.


Daichi Enomoto, Masanori Obana, Akimitsu Miyawaki, Makiko Maeda, Hiroyuki Nakayama, Yasushi Fujio Cardiac-specific ablation of the STAT3 gene in the subacute phase of myocardial infarction exacerbated cardiac remodeling Am J Physiol Heart Circ Physiol, published August 1, 2015, DOI: 10.1152/ajpheart.00730.2014.

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