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


miR140 and Right Heart Hypertrophy

Is there one microRNA playing a primary role in the complex pathogenesis of right ventricular failure caused by pulmonary hypertension? Listen as Associate Editor Fabio Recchia (Temple University Lewis Katz School of Medicine, and Scuola Superiore Sant'Anna, Pisa, Italy) interviews lead author Sachin Gupte (New York Medical College) and content expert Paras Mishra (University of Nebraska Medical Center) about the work by Joshi et al, which used microarray analysis to focus on MiR140 as a potential therapeutic target in a Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension (PAH). Is MiR31 also a major player in the pathogenesis of this disease? What is the translational relevance of the work by Gupte and colleagues on afterload-induced right ventricular failure? Listen to find out.

Sachindra Raj Joshi, Vidhi Dhagia, Salina Gairhe, John G. Edwards, Ivan F. McMurtry, Sachin A Gupte MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/Hypoxia/Normoxia model of pulmonary arterial hypertension Am J Physiol Heart Circ Physiol, published July 15, 2016. DOI: 10.1152/ajpheart.00264.2016


AngII and Aging-Induced Endothelial Dysfunction

Aging, as we all know, is unavoidable and leads to an increased risk for vascular dysfunction and cardiovascular pathologies. So what are the mechanisms responsible for aging-induced vascular dysfunction? That’s just what Flavahan et al set out to investigate in their latest work in AJP-Heart and Circ. Listen as Editor in Chief Dr. Irving H. Zucker (University of Nebraska Medical Center) interviews lead author Nick Flavahan (Johns Hopkins University) and content expert Edward Lakatta (National Institute on Aging, National Institutes of Health) about Flavahan’s work, which builds on previous studies by Lakatta. Chronic in vivo inhibition of angiotensin activity protects endothelial function, but is it due to blockade of the systemic Renin-Agiotensin System (RAS) or the local vascular angiotensin system? What role do changes in anti-oxidant scavenging mechanisms play in endothelial dysfunction associated with aging? How do flow-mediated dilation and changes in angiotensin receptor expression fit into the big picture of aging? Listen and find out.

Sheila Flavahan, Fumin Chang, Nicholas A. Flavahan Local Renin-Angiotensin System Mediates Endothelial Dilator Dysfunction in Aging Arteries Am J Physiol Heart Circ Physiol, published July 15, 2016. DOI: 10.1152/ajpheart.00422.2016


Sympathetic Reactivity and Family History of Hypertension

How does family history of hypertension contribute to sympathetic neural control of blood pressure, and what role does mental stress play in blood pressure regulation? The latest work by Fonkue et al seeks to answer these very questions. Listen as Consulting Editor Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine) interviews lead author Jason Carter (Michigan Technological University) and content expert Megan Wenner (University of Delaware) about the study by Carter and colleagues, which used microneurography to measure muscle sympathetic nerve activity (MSNA) during an acute bout of mental stress (performing mental math) in both women and men with, and without, a family history of hypertension. Can evaluations of larger groups over several years help determine if the sympathetic nervous system plays an essential role in the development of hypertension in those with a family history of the disease? Listen and find out.

Ida T. Fonkoue, Min Wang, Jason R. Carter Sympathetic neural reactivity to mental stress in offspring of hypertensive parents: 20 years revisited Am J Physiol Heart Circ Physiol, published July 1, 2016. DOI: 10.1152/ajpheart.00378.2016


Vascular Health After Preeclampsia

What is the mechanism behind the increased risk for cardiovascular and renal diseases in women who have previously suffered from early-onset preeclampsia? Listen as Associate Editor Robert Hester (University of Mississippi Medical Center) interviews lead author Anne Marijn van der Graaf (University of Groningen Medical Center) and content expert Ira Bernstein (University of Vermont Medical Center) about the clinical study by van der Graaf and colleagues, which compared the arterial stiffness of healthy women with a history of preeclamptic pregnancy to healthy women with no preeclamptic pregnancy history after low sodium and high sodium diets. Were formerly preeclamptic women able to adjust their arterial stiffness after eating a low sodium diet? What is the role of vessel wall function and the glycocalyx as markers of vascular stiffness? Listen and find out.

Anne Marijn van der Graaf, Nina D. Paauw, Tsjitske J. Toering, Martin Feelisch, Marijke M. Faas, Thomas R. Sutton, Magdalena Minnion, Joop D. Lefrandt, Sicco A. Scherjon, Arie Franx, Gerjan Navis, A. Titia Lely Impaired sodium-dependent adaptation of arterial stiffness in formerly preeclamptic women: the RETAP-vascular study Am J Physiol Heart Circ Physiol, published June 1, 2016. DOI: 10.1152/ajpheart.00010.2016