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


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


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


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


Role of FOXO3a in Heart Failure

Does the transcription factor FOXO3a regulate BNIP3 gene expression in the heart? In this podcast, Associate Editor Ajay Shah (King’s College London) interviews lead author Antoine Chaanine (Mayo Clinic) and content expert Christoph Maack (Universitatsklinikum des Saarlandes) about the new work by Chaanine and co-authors exploring whether FOXO3a plays a role in mitochondrial dysfunction and myocardial remodeling via BNIP3. Looking at both myocytes and in vivo responses, the authors focus on the microdomain between the sarcoplasmic reticulum and the mitochondria, as well as the intricate balance of SR calcium release and mitochondrial calcium uptake. Is the FOXO3a-BNIP3 pathway involved in diastolic dysfunction in heart failure, or is the primary effect on adverse myocardial remodeling which in turn affects end-diastolic function? Listen to find out.


Antoine Heni Chaanine, Erik Kohlbrenner, Scott I. Gamb, Adam J. Guenzel, Katherine A. Klaus, Ahmed U. Fayyaz, K Sreekumaran Nair, Roger J. Hajjar, Margaret M. Redfield FOXO3a Regulates BNIP3 and Modulates Mitochondrial Calcium, Dynamics and Function in Cardiac Stress Am J Physiol Heart Circ Physiol, published September 30, 2016. DOI: 10.1152/ajpheart.00549.2016


Heart Rate Modeling

Can increasing heart rate in patients with heart failure with preserved ejection fraction (HFpEF) improve outcomes? Yes, according to the new study by Klein et al. In this podcast Associate Editor Fabio Recchia (Temple University Lewis Katz School of Medicine, and Scuola Superiore Sant'Anna, Pisa, Italy) interviews lead author Markus Meyer (University of Vermont College of Medicine) and content expert Jonathan Kirk (Loyola University Chicago) about the work by Meyer and co-authors, which challenges the “canonical thought” of heart pacing in HFpEF patients. Using a large animal model of HFpEF, and taking key inspiration from a unique bedside-to-bench experience, Meyer and colleagues found that two weeks of cardiac pacing at a fixed rate 30 beats per minute above spontaneous heart rate in pigs resulted in slightly increased heart chamber volumes, but reduced left ventricular wall thickness, decreased myocardial fibrosis, and improved diastolic compliance. Does this approach improve left ventricular response to stress? Listen and learn.


Franziska J. Klein, Stephen Bell, K. Elisabeth Runte, Robert Lobel, Takamuru Ashikaga, Lilach O. Lerman, Martin M. LeWinter, Markus Meyer Heart rate-induced modifications of concentric left ventricular hypertrophy: exploration of a novel therapeutic concept Am J Physiol Heart Circ Physiol, published October 1, 2016. DOI: 10.1152/ajpheart.00301.2016


TNF and Cardiac Stem Cell Differentiation

Why is the post- myocardial infarction micro environment of the heart so hostile for cardiac stem cells? In this podcast, Deputy Editor Merry Lindsey (University of Mississippi Medical Center) interviews lead author Sumanth Prabhu (University of Alabama at Birmingham) and content expert Richard Gumina (Vanderbilt University) about the work by Hamid et al, which determined that tumor necrosis factor (TNF) signaling inhibits endogenous cardiac stem cell repair and blunts stem cell treatment efficacy in human heart failure. What relationship did Prabhu and co-authors uncover between TNF-alpha and adrenergic activation? How did the authors manage the biological variability of primary stem cell isolates in their technically nuanced study? Finally, if “timing is everything” holds true, does this study provide a clinical translation roadmap for timing TNF receptor blockade post-MI? Listen to learn more.

Tariq Hamid, Yuanyuan Xu, Mohamed Ameen Ismahil, Qianhong Li, Steven P. Jones, Aruni Bhatnagar, Roberto Bolli, Sumanth D. Prabhu TNF receptor signaling inhibits cardiomyogenic differentiation of cardiac stem cells and promotes a neuroadrenergic-like fate Am J Physiol Heart Circ Physiol, published November 1, 2016. DOI: 10.1152/ajpheart.00904.2015


Myocardial Dysfunction in Prediabetes

What are the functional and molecular mechanisms underlying prediabetes? Listen as Consulting Editor Michael Wolin (New York Medical College) interviews lead author Zoltan Giricz (Semmelweis University, Hungary) and content expert Hemal Patel (VA San Diego Healthcare System, University of California, San Diego) about the intriguing new work by Koncsos et al, which used a non-genetic rodent model of prediabetes to assess the deterioration of cardiac function in prediabetes caused by disturbances in multiple cellular processes, including mitochondrial oxidative stress. Why did the authors choose a high-fat diet model rather than a genetic model of prediabetes? Is oxidant stress at the sub-sarcolemmal mitochondria level the trigger point for downstream cardiovascular dysfunction? Listen and learn.

Gábor Koncsos, Zoltan V Varga, Tamas Baranyai, Kerstin Boengler, Susanne Rohrbach, Ling Li, Klaus-Dieter Schluter, Rolf Schreckenberg, Tamás Radovits, Attila Oláh, Csaba Mátyás, Árpád Lux, Mahmoud Al-Khrasani, Tímea Komlódi, Nóra Bukosza, Domokos Máthé, László Deres, Monika Barteková, Tomáš Rajtík, Adriana Adameová, Krisztián Szigeti, Péter Hamar, Zsuzsanna Helyes, László Tretter, Pal Pacher, Béla Merkely, Zoltán Giricz, Rainer Schulz, Péter Ferdinandy Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress Am J Physiol Heart Circ Physiol, published October 1, 2016. DOI: 10.1152/ajpheart.00049.2016


Right Ventricular Metabolic Adaptations to Exercise Training

What exactly is happening in the metabolism of the exercising individual? Listen as Associate Editor Gary Lopaschuk (University of Alberta, Canada) interviews lead author Kari Kalliokoski (University of Turku, Finland) and content expert Michael Nelson (University of Texas at Arlington) about the work by Heiskanen et al, which studied energy metabolism in the heart during cardiac hypertrophy that was not pathological, but rather a result of exercise. Kalliokoski and colleagues measured changes in myocardial metabolism for healthy, untrained individuals who participated in either high intensity interval training (HIIT) or moderate intensity continuous aerobic training. Using PET imaging, once with a euglycemic hyperinsulinemic clamp and once in a traditional fasting state, Kalliokoski and co-authors studied the right ventricular response to exercise and its training adaptation. Did the HIIT training group achieve better results with just 3 minutes of exercise, compared to the moderate intensity aerobic group which exercised 40 – 60 minutes? Listen now.

Marja A. Heiskanen, Tuija Leskinen, Ilkka H. A. Heinonen, Eliisa Löyttyniemi, Jari-Joonas Eskelinen, Kirsi Virtanen, Jarna C. Hannukainen, Kari K. Kalliokoski Right ventricular metabolic adaptations to high-intensity interval and moderate-intensity continuous training in healthy middle-aged men Am J Physiol Heart Circ Physiol, published September 1, 2016. DOI: 10.1152/ajpheart.00399.2016


Habitual Exercise and Systolic Blood Pressure During Resistance Exercise

Elevations in systolic blood pressure during both resistance and cardiovascular exercise, and during regular daily activities, are predictive in the development of cardiovascular disease. Can higher levels of general physical activity reduce the rise in systolic blood pressure that occurs with resistance exercise? Listen as Consulting Editor David Gutterman (Medical College of Wisconsin) interviews lead author Takeshi Otsuki (Ryutsu Keizai University, Japan) and content expert Shane Phillips (University of Illinois-Chicago) about the work by Otsuki and colleagues which combined both observational and interventional human studies involving moderate intensity exercise programs. Is blood pressure during exercise a more sensitive predictor of cardiovascular risk than resting blood pressure? Does brachial arterial stiffness affect blood pressure during exercise? Listen and find out.

Takeshi Otsuki, Takahiro Kotato, Asako Zempo-Miyaki Habitual exercise decreases systolic blood pressure during low-intensity resistance exercise in healthy middle-aged and older individuals Am J Physiol Heart Circ Physiol, published October 1, 2016. DOI: 10.1152/ajpheart.00379.2016