Macrophage MMP-9 Accelerates Cardiac Aging

Is macrophage MMP-9 a prime upstream regulator of cardiac aging? Yes, according to new research by Toba et al, explored in our latest podcast. Editor in Chief Irving H. Zucker (University of Nebraska Medical Center) interviews lead author and Deputy Editor Merry Lindsey (University of Mississippi Medical Center) and content expert Richard Gumina (Vanderbilt University) about the work by Lindsey and colleagues, which expands our knowledge of macrophage MMP-9 overexpression and its amplification of the myocyte hypertrophic response to aging. Did Lindsey and co-authors find in their experimental model that diastolic cardiac physiology was impaired before systolic cardiac physiology? MMP-9 appears to be a driver of inflammation, rather than a consequence of inflammation. Does MMP-9 in the aged heart also play a pro-fibrogenic role? Listen and learn more.

 

Hiroe Toba, Presley L. Cannon, Andriy Yabluchanskiy, Rugmani Padmanabhan Iyer, Jeanine D’Armiento, Merry L. Lindsey Transgenic overexpression of macrophage matrix metalloproteinase-9 exacerbates age-related cardiac hypertrophy, vessel rarefaction, inflammation, and fibrosis Am J Physiol Heart Circ Physiol, published March 1, 2017. DOI:10.1152/ajpheart.00633.2016

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Genes and Vascular Reactions to Diving

Is the vascular response in humans to the diving reflex genetically determined? In our first-ever podcast recorded in both Russian and English, Associate Editor Debra I. Diz (Wake Forest University School of Medicine) interviews lead author Tatiana I. Baranova (St.-Petersburg State University, Russia), her translator Vladimir Boykov, and content expert Charles E. Wood (University of Florida). Listen as we explore the work by Baranova and co-authors, which determined that polymorphisms in the bradykinin and renin-angiotensin systems are the driving force behind hemodynamic responses to the diving reflex. What is known about the functional implications of the mutations that affect the coding regions of the genes ADBR2, ACE, AGTR1, BDKRB2, and REN? Does this work on the genomics of hemodymic changes during transient hypoxia have potential therapeutic applications in personalized medicine? Listen to find out.

 

Tatiana I. Baranova, Dmitrii N. Berlov, Oleg S. Glotov, Ekaterina A. Korf, Alexey D. Minigalin, Alla V. Mitrofanova, Ildus I Ahmetov, Andrey S. Glotov Genetic determination of the vascular reactions in humans in response to the diving reflex Am J Physiol Heart Circ Physiol, published online December 6, 2016. DOI: 10.1152/ajpheart.00080.2016

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Sympathetic Nerves and Cardiac Propagation

What are the mechanisms by which sympathetic nerve activity triggers ventricular arrhythmia? Listen as Consulting Editor Crystal Ripplinger (University of California Davis) interviews lead author Olujimi Ajijola (University of California Los Angeles) and content expert Christian Meyer (University Heart Centre Hamburg) about this key question explored in the innovative work by Ajijola et al. In a chronically infarcted porcine model, Ajijola and co-authors investigated whether sympathetic activity modulated activation and conduction in normal hearts and post myocardial infarction. The authors found that right stellate stimulation had a stronger effect than left in normal hearts. Was the same true after myocardial infarction? Do the clinical implications of modulation of late potentials during sympathetic stimulation suggest that clinicians need to rethink their ablation mapping techniques? Listen and learn.

 

Olujimi A. Ajijola, Robert L Lux, Anadjeet Khahera, OhJin Kwon, Eric Aliotta, Daniel Ennis, Michael C. Fishbein, Jeffrey Laurence Ardell, Kalyanam Shivkumar Sympathetic Modulation of Electrical Activation In Normal and Infarcted Myocardium: Implications for Arrhythmogenesis Am J Physiol Heart Circ Physiol, published online January 13, 2017. DOI: 10.1152/ajpheart.00575.2016

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Cerebroarterial Dysfunction in Swedish-Arctic AD Mice

In a true chicken-and-egg question, can researchers accurately pinpoint if cerebrovascular pathology or Alzheimer's disease (AD) present sequentially or simultaneously? Listen as Guest Editor Vincenzo Lionetti (Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy) interviews lead author Mario Merlini (University of Zurich, Switzerland, and Gladstone Institute of Neurological Disease, UCSF) and content expert Roy Weller (University of Southampton School of Medicine) about the novel work by Merlini et al that seeks to untangle the complicated web of cerebrovascular pathology, AD pathology, and vascular dementia, as well as neuronal and endothelial tau pathology. In this extended podcast, we speculate on the role that endothelial tau may play in disrupting nitric oxide synthase in the nucleus. Our experts consider whether endothelial dysfunction at the onset of AD is a gene or age-dependent phenomenon. Why did Merlini and co-authors use histology to investigate the loss of cyclic-GMP in the absence of amyloid deposits in the basilar artery? Does the Swedish-Arctic mouse model accurately reflect the AD clinical condition? Listen to this intriguing conversation and find out.

 

Mario Merlini, Yi Shi, Stephan Keller, Gianluigi Savarese, Alexander Akhmedov, Rebecca Derungs, Remo D. Spescha, Luka Kulic, Roger M. Nitsch, Thomas F. Lüscher, Giovanni G. Camici Reduced nitric oxide bioavailability mediates cerebroarterial dysfunction independent of cerebral amyloid angiopathy in a mouse model of Alzheimer’s disease Am J Physiol Heart Circ Physiol, published February 1, 2017. DOI: 10.1152/ajpheart.00607.2016

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Renin-Angiotensin System Signaling in Aged and Age-Exercised Rats

Does aging influence myocardial angiotensin II levels in the heart? Listen as Editor in Chief Irving H. Zucker (University of Nebraska Medical Center) interviews lead author Dong Sun (New York Medical College) and content expert Zsolt Bagi (Augusta University) about the recent study by Froogh et al, which compared three experimental groups (young sedentary, aged sedentary, and aged exercising rats) to determine why there is a mismatch between angiotensin II and angiotensin 1 – 7 in the aged heart. Does perivascular chymase and angiotensin production specifically target blood vessels? What do the authors speculate is the mechanisms by which exercise can alter ACE and ACE 2, including chymase? Find out this and more. Listen now.

 

Ghezal Froogh, John T Pinto, Yicong Le, Sharath Kandhi, Yeabsra Aleligne, An Huang, Dong Sun Chymase-dependent production of angiotensin II: an old enzyme in old hearts Am J Physiol Heart Circ Physiol, published online November 4, 2016. DOI: 10.1152/ajpheart.00534.2016

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Parental Vitamin D Deficiency Increases BP in Offspring

Do we really know the potential effects of maternal, and paternal, diets on offspring genotype and phenotype? In this podcast, Associate Editor Nancy Kanagy (University of New Mexico School of Medicine) interviews lead author Rudolf de Boer (University Medical Center Groningen) and content expert Mingyu Liang (Medical College of Wisconsin) about the exciting new work by Meems et al which investigated the cardiovascular effects on offspring born to vitamin D deficient parents. While the initial idea for this work by de Boer and colleagues sprang from the well-documented clinical observation that Dutch people born to parents who survived the post- World War II famine have excess cardiovascular risk, the study opens the door to discuss vitamin D and other dietary deficiency multi-generational effects on offspring. Is there a consensus among researchers on how to analyze epigenetic methylation data? Listen and find out.

 

Laura M. G. Meems, Hasan Mahmud, Hendrik Buikema, Jörg Tost, Sven Michel, Janny Takens, Rikst N. Verkaik-Schakel, Inge Vreeswijk-Baudoin, Irene V. Mateo-Leach, Pim van der Harst, Torsten Plösch, Rudolf A. de Boer Parental vitamin D deficiency during pregnancy is associated with increased blood pressure in offspring via Panx1 hypermethylation Am J Physiol Heart Circ Physiol, published online December 1, 2016. DOI: 10.1152/ajpheart.00141.2016

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Mitochondrial Dynamics Impact Endothelial Function

What role does mitochondrial fragmentation play in endothelial dysfunction under conditions of low glucose? Listen as Consulting Editor Michael Wolin (New York Medical College) interviews lead author Michael Widlansky (Medical College of Wisconsin) and content expert Prasad Katakam (Tulane University School of Medicine) about the new work by Tanner et al which investigated the often-overlooked condition of low glucose in humans. Does the mitochondrial fission protein dynamin-related protein 1 (DRP1) regulate vascular endothelial function through ROS production? Our experts explore the work by Widlansky and colleagues that leads to new and engaging open questions. How is DRP1 activated and what docking proteins may be involved? Listen and find out.

 

Michael John Tanner, Jingli Wang, Rong Ying, Tisha B Suboc, Mobin Malik, Allison Couillard, Amberly Branum, Venkata Puppala, Michael Eric Widlansky Dynamin-Related Protein 1 Mediates Low Glucose-Induced Endothelial Dysfunction in Human Arterioles Am J Physiol Heart Circ Physiol, published online December 6, 2016. DOI: 10.1152/ajpheart.00499.2016

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TLR9 in Post-Infarct Cardiac Rupture

Is myocardial rupture in acute myocardial infarction preventable? Perhaps, according to new research by Omiya et al into the mechanisms underlying myocardial rupture in a toll-like receptor 9 knockout mouse model compared to a permanent coronary ligation model. In this podcast, Associate Editor Junichi Sadoshima (Rutgers New Jersey Medical School) interviews lead author Kinya Otsu (King's College London British Heart Foundation Centre of Excellence) and content expert Richard Kitsis (Albert Einstein College of Medicine) about the work by Otsu and colleagues exploring why toll-like receptor 9 shows cardioprotective effects on myocardial rupture but does not play a role in inflammation. Why are myocardial fibroblasts affected but inflammatory cells are not affected by TLR-9 knockout, and what exactly is the role of myofibroblasts in preventing cardiac rupture? What are the clinical implications for acute MI patients going forward? Listen and find out.

 

Shigemiki Omiya, Yosuke Omori, Manabu Taneike, Andrea Protti, Osamu Yamaguchi, Shizuo Akira, Ajay M. Shah, Kazuhiko Nishida, Kinya Otsu Toll-like receptor 9 prevents cardiac rupture after myocardial infarction in mice independently of inflammation Am J Physiol Heart Circ Physiol, published online December 1, 2016. DOI: 10.1152/ajpheart.00481.2016

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Metaboreflex-induced Functional Coronary Vasoconstriction

How does the muscle metaboreflex work to regulate coronary blood flow during exercise, particularly in the cardiovascular disease state of hypertension? Listen as Editor in Chief Irving H. Zucker (University of Nebraska Medical Center) interviews lead author Donal O’Leary (Wayne State University School of Medicine) and content expert David Stepp (Augusta University) about the large animal study conducted by O’Leary and colleagues, a technical tour de force which explored whether blocking an increase in vasoconstriction due to increased sympathetic activity in the heart would actually increase coronary blood flow and increase ventricular function. Does this elegant study make the case for focusing on coronary blood flow, rather than blood pressure, as a potential therapeutic target for the treatment of hypertension? Listen to find out.

 

Marty D. Spranger, Jasdeep Kaur, Javier A. Sala-Mercado, Abhinav C. Krishnan, Rania Abu-Hamdah, Alberto Alvarez, Tiago M. Machado, Robert A. Augustyniak, Donal S. O'Leary Exaggerated coronary vasoconstriction limits muscle metaboreflex-induced increases in ventricular performance in hypertension Am J Physiol Heart Circ Physiol, published online October 21, 2016. DOI: 10.1152/ajpheart.00417.2016

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Acute Progesterone Modifies Cardiac Contraction

If cardiovascular scientists use only male animals in animal model studies, will important observations be missed? Yes, according to a new study by Feridooni et al. In this podcast, Editor in Chief Irving H. Zucker interviews lead author Susan Howlett (Dalhousie University, Canada) and content expert Lea Delbridge (University of Melbourne, Australia) about the work by Howlett and colleagues which explored the acute effects of progesterone on the heart. The key finding is that in female mouse hearts—but not in male mouse hearts—progesterone markedly slowed and attenuated contractions in multicellular ventricular muscle, but had no effect on the underlying calcium transients. This surprising data might never have been discovered if Howlett and colleagues had conducted their experiments only on male mice. Does the estrous cycle in female rodents create physiological heterogeneity that is too confounding to experimentally overcome? Does the negative inotropic impact of progesterone shown in vitro translate to the in vivo setting? Listen and learn more.

 

Hirad A Feridooni, Jennifer K MacDonald, Anjali Ghimire, W. Glen Pyle, Susan E. Howlett Acute exposure to progesterone attenuates cardiac contraction by modifying myofilament calcium sensitivity in the female mouse heart Am J Physiol Heart Circ Physiol, published online October 28, 2016. DOI: 10.1152/ajpheart.00073.2016

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