AJP - Heart and Circulatory Physiology

Neuregulin1/ErbB4 Signaling and Cardiomyocyte Proliferation

khkeehan — Wed, 02 May 2012 15:32:42 +0000

How is cardiac neuregulin signaling involved after herceptin treatment of breast cancer patients? Our latest podcast explores the new Review article by Wadugu et al, which focuses on neuregulin signaling in the heart and dissects early observations that up to 30% of patients treated with herceptin for breast cancer displayed heart failure as a side-effect, likely by inhibiting neuregulin signaling. Cardiomyocyte proliferation is just one of many events triggered by neuregulin activation in heart cells, thereby opening a safe, paracrine possibility to stimulate myocyte proliferation in experimental and clinical heart failure studies. Listen as Associate Editor Leon de Windt talks with senior author Bernhard Kuhn (Children’s Hospital Boston/Harvard Medical School) and leading expert Douglas Sawyer (Vanderbilt University) about stem cell treatments, clinical trials, and much more.

Brian Wadugu and Bernhard Kuhn. The role of neuregulin/ErbB2/ErbB4 signaling in the heart with special focus on effects on cardiomyocyte proliferation Am J Physiol Heart Circ Physiol, published ahead of print March 16, 2012, doi: 10.1152/ajpheart.00063.2012.

O-GlcNAc Signaling During Hypertrophy

khkeehan — Tue, 24 Apr 2012 14:37:39 +0000

Does protein glycosylation drive cardiac hypertrophy? In our latest podcast, Editor in Chief William Stanley talks with senior author Steven P. Jones (University of Louisville) and leading expert John Chatham (University of Alabama at Birmingham) to discuss the work by Facundo et al that explores the role of O-GlcNAc in pathological cardiac hypertrophy through NFAT modification. Listen as they discuss the complexities and importance of O-GlcNAc signaling, and explore the methodological challenges in assessing protein O-GlcNAcylation. Is there a role in heart failure or diabetic cardiomyopathy? Listen in and find out.

Heberty T. Facundo, Robert E. Brainard, Lewis J Watson, Gladys A. Ngoh, Tariq Hamid, Sumanth D. Prabhu, and Steven P. Jones O-GlcNAc Signaling is Essential for NFAT-Mediated Transcriptional Reprogramming During Cardiomyocyte Hypertrophy Am J Physiol Heart Circ Physiol, published ahead of print March 9, 2012, doi: 10.1152/ajpheart.00775.2011.

Mitochondrial Adaptations and Myocardial Energetics

khkeehan — Fri, 13 Apr 2012 17:40:09 +0000

The protective effect of ischemic preconditioning lasts for only a few hours, then reappears about a day later in what is termed the Second Window of Protection (SWOP). In this podcast Editor in Chief William Stanley interviews senior author Edward McFalls (VA Medical Center, University of Minnesota) and leading expert Nazareno Paolocci (Johns Hopkins University) about the work by Cabrera et al, which brings together an elegant animal model, cutting-edge proteomics technology, and clinical cardiologist and cardiovascular physiologist to uncover the role of the mitochondria and energetics in mediating SWOP.

Jesus A Cabrera, Elizabeth A Ziemba, Robert Colbert, Lorraine Anderson, Willem Sluiter, Dirk J. Duncker, Tammy A Butterick, Joseph Sikora, Herbert B Ward, Rosemary F Kelly, and Edward O McFalls. Altered Expression of Mitochondrial Electron Transport Proteins and Improved Myocardial Energetic State During Late Ischemic Preconditioning Am J Physiol Heart Circ Physiol, published ahead of print March 2, 2012, doi: 10.1152/ajpheart.00372.2011.

Photoplethysmography with Valsalva Maneuver Reflects Filling Pressure

khkeehan — Thu, 12 Apr 2012 13:45:43 +0000

What do Valsalva, the 17th century Italian physician, and smartphones have in common? Listen to our latest intriguing podcast which explores how the Valsalva Maneuver, when paired with finger photoplethysmography using a simple pulse oximetry probe, may provide cardiologists with an alternative to cardiac catheterization for heart failure patients. Associate Editor Ajay Shah interviews lead author Harry Silber (Johns Hopkins University) and expert Charles Chung (University of Arizona) about the work by Silber and colleagues, which knits together classical cardiovascular physiology, clinical cardiology, and inventive uses of existing technologies to provide insights into the left ventricular filling pressure of heart failure patients.

Harry A. Silber, Jeffrey C. Trost, Peter V. Johnston, W. Lowell Maughan, Nae-Yuh Wang, Edward K. Kasper, Thomas R. Aversano, and David E. Bush. Finger Photoplethysmography During the Valsalva Maneuver Reflects Left Ventricular Filling Pressure Am J Physiol Heart Circ Physiol, published ahead of print March 2, 2012, doi: 10.1152/ajpheart.00609.2011.

Hemin toxicity and autophagy

khkeehan — Tue, 03 Apr 2012 17:55:17 +0000

We know that hemin toxicity effects vascular endothelial cells, which may contribute to cardiovascular diseases. But what is the underlying molecular mechanism? In our newest podcast, Associate Editor Christine des Rosiers interviews senior author Victor Darley-Usmar (University of Alabama at Birmingham) and leading expert Neil Hogg (Medical College of Wisconsin) about the connections between lipid peroxidation in cells and its damaging effects on mitochondrial function, and the role autophagy may play in protecting those mitochondria from damage.

Ashlee N. Higdon, Gloria A. Benavides, Balu K. Chacko, Xiaosen Ouyang, Michelle S. Johnson, Aimee Landar, Jianhua Zhang, Victor M. Darley-Usmar. Hemin causes mitochondrial dysfunction in endothelial cells through promoting lipid peroxidation: the protective role of autophagy Am J Physiol Heart Circ Physiol, published online April 1, 2012, doi: 10.1152/ajpheart.00584.2011.

Nerve induced EC Ca2+ signals oppose vasoconstriction

khkeehan — Wed, 14 Mar 2012 15:54:54 +0000

Our latest podcast takes us into the realm of calcium pulsars. Associate Editor Nancy Kanagy talks with senior author Mark Nelson (University of Vermont) and leading expert Michael Hill (University of Missouri) about how the work of Nausch et al challenges the traditional view that the sympathetic nervous system regulates vascular tone independent of the endothelium. This work by Nelson and colleagues shows that the endothelium is dynamically engaged during neurovascular coupling through transcellular negative feedback which limits vasoconstriction. Listen as we explore how the vascular smooth muscle communicates with the endothelium, and the potential significance of this EDH mechanism to oppose sympathetically-mediated constriction.

Lydia W. M. Nausch, Adrian D. Bonev, Thomas J. Heppner, Yvonne Tallini, Michael I. Kotlikoff, Mark T. Nelson. Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries Am J Physiol Heart Circ Physiol, published ahead of print December 2, 2011, doi:10.1152/ajpheart.00773.2011.

In pursuit of scientific excellence - sex matters

khkeehan — Tue, 28 Feb 2012 15:46:50 +0000

Sex and gender matter in physiology, but are frequently ignored in scientific publications. In our latest podcast, Editor in Chief William Stanley has a lively conversation with leading experts Virginia Miller (Mayo Clinic) and Jane Reckelhoff (University of Mississippi) about the importance of sex and gender differences in physiology research and publications. Clear sex differences are apparent at the molecular, cellular and whole organ levels, prompting a new editorial policy for the American Physiological Society publications which requires reporting of the sex and/or gender of animals and humans, as well as all derived materials. Learn about how to approach this important issue in your work, and the surprising effects of sex on physiology from the molecular level on up.

Virginia M. Miller. In pursuit of scientific excellence - sex matters Am J Physiol Heart Circ Physiol, published ahead of print February 10, 2012, doi: 10.1152/ajpheart.00073.2012.

Fructose diet-induced cardiomyocyte Ca2+ cycling abnormality

khkeehan — Thu, 09 Feb 2012 17:36:49 +0000

In our latest podcast we explore the cardiac-specific effects of a high fructose diet. An inventive new study by Mellor et al investigates excitation contraction coupling changes in myocytes isolated from an experimental mouse model. These studies reveal, upon high fructose feeding, marked alterations in myocyte Ca2+ handling, but with maintained contractile function. Associate Editor Meredith Bond and leading expert Susan Howlett (Dalhousie University) interview senior author Lea Delbridge (University of Melbourne) about her exciting new work on diabetic cardiomyopathy.

Kimberley M Mellor, Igor R Wendt, Rebecca H Ritchie, and Lea M.D. Delbridge. Fructose diet treatment in mice induces fundamental disturbance of cardiomyocyte Ca2+ handling and myofilament responsiveness Am J Physiol Heart Circ Physiol, published ahead of print December 23, 2011, doi:10.1152/ajpheart.00797.2011.

Molecular mechanisms linking salt to hypertension

khkeehan — Mon, 06 Feb 2012 19:15:48 +0000

It is well known that there is no single cause of hypertension, but many of the factors that contribute to hypertension are known. Our latest podcast spotlights an elegant new Review article by Blaustein and colleagues which focuses on the interplay of salt and the secretion and action of endogenous ouabain. Associate Editor Irving Zucker interviews senior author, and fellow Associate Editor, Mordecai Blaustein (University of Maryland), along with leading expert John Osborn (University of Minnesota) about how endogenous ouabain might contribute to salt-sensitive hypertension and plays a central role in the alterations in the central nervous system, kidney and vasculature which contribute to chronic hypertension.

Mordecai P. Blaustein, Frans HH Leenen, Ling Chen, Vera A. Golovina, John M Hamlyn, Thomas L Pallone, James W. Van Huysse, Jin Zhang, Withrow Gil Wier. How NaCl raises blood pressure: A new paradigm for the pathogenesis of salt-dependent hypertension Am J Physiol Heart Circ Physiol, published ahead of print November 4, 2011, doi:10.1152/ajpheart.00899.2011.

BH4 and Vascular Function in Women

khkeehan — Thu, 02 Feb 2012 18:04:56 +0000

What’s the problem with arterial function following menopause? Listen as Editor in Chief William Stanley, senior author Kerrie Moreau (University of Colorado Denver), and leading women’s health expert Virginia Miller (Mayo Clinic) engage in a lively conversation about the latest clinical study by Moreau et al on the role of estrogen and uncoupled nitric oxide synthase in arterial stiffening in post-menopausal women. Can early intervention with estrogen combat accelerated vascular aging after menopause?

Kerrie L Moreau, Amie Meditz, Kevin Deane, Wendy M. Kohrt. Tetrahydrobiopterin Improves Endothelial Function and Decreases Arterial Stiffness in Estrogen-Deficient Postmenopausal Women Am J Physiol Heart Circ Physiol, published ahead of print January 13, 2012, doi:10.1152/ajpheart.01065.2011.

Obesity and orthopedic trauma

khkeehan — Wed, 18 Jan 2012 19:00:05 +0000

The obesity epidemic in the United States shows no signs of abating, which is why our latest podcast is particularly insightful. Associate Editor Nancy Kanagy talks with author Lusha Xiang (University of Mississippi) and leading expert Jeff Frisbee (West Virginia University) about the study by Xiang and colleagues, which suggests the mechanism behind the poor prognosis for obese trauma victims and provides insight into a new therapeutic intervention to improve recovery of obese victims of traumatic injury.

Lusha Xiang, Silu Lu, William Fuller, Arun Aneja, George V Russell, Louis B Jones, and Robert L. Hester. Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma. Am J Physiol Heart Circ Physiol, published ahead of print October 14, 2011, doi: 10.1152/ajpheart.00439.2011.

Muscle oxygen transport and utilization in heart failure

khkeehan — Wed, 11 Jan 2012 18:20:16 +0000

A well-known problem for heart failure patients is the inability, or markedly decreased ability, to exercise. When even low levels of daily activity are impaired, the quality of life for heart failure patients suffers considerably. The mechanisms for exercise intolerance are very complicated and extend far beyond impaired cardiac performance. Listen in as Associate Editor Irving Zucker, senior author David Poole (Kansas State University) and leading expert Peter Wagner (University of California, San Diego) discuss the new Review article by Poole and colleagues, which tackles the mechanisms of muscle dysfunction in heart failure at the oxygen transport and microcirculatory levels.

David C. Poole, Daniel M. Hirai, Steven W. Copp, and Timothy I. Musch. Muscle Oxygen Transport and Utilization in Heart Failure: Implications for Exercise (In)tolerance Am J Physiol Heart Circ Physiol, published ahead of print November 18, 2011, doi:10.1152/ajpheart.00943.2011.

Interstitial Volume Modulates the Conduction Velocity- Gap Junction Relationship

khkeehan — Fri, 06 Jan 2012 15:26:04 +0000

What are the parameters which modulate conduction under normal and disease conditions in the heart? This age-old debate has pitted two distinct schools of thought against each other—ephaptic conduction vs. gap junctions. Can changes in interstitial volume by pharmacological means dramatically change conduction velocity? In our latest podcast on the article by Veeraraghavan et al, Associate Editor Igor Efimov, leading expert Craig Henriquez (Duke University) and senior author Steven Poelzing (University of Utah) wade into the debate.

Rengasayee Veeraraghavan, Mohamed E. Salama, and Steven Poelzing. Interstitial volume modulates the conduction velocity-gap junction relationship. Am J Physiol Heart Circ Physiol, published ahead of print October 21, 2011, doi: 10.1152/ajpheart.00868.2011.

Mitofusin-1 Deficiency in the Heart

khkeehan — Tue, 13 Dec 2011 19:01:41 +0000

Our latest podcast focuses on mitochondrial dynamics, as senior author Ken Walsh (Boston University) and expert Elizabeth “Tish” Murphy (NHLBI) join Consulting Editor Michael Wolin to discuss the recent study by Papanicolau et al, showing surprising effects of cardiac deletion of the key mitochondrial membrane protein mitofusin-1. Listen in as we uncover the unexpected impact of mitofusin-1 and mitofusin-2 on mitochondrial size and resistance to stress.

Kyriakos N. Papanicolaou, Gladys A. Ngoh, Errine R Dabkowski, Kelly A O’Connell, Rogerio F. Ribeiro, William C. Stanley, and Kenneth Walsh. Cardiomyocyte deletion of mitofusin-1 leads to mitochondrial fragmentation and improves tolerance to ROS-induced mitochondrial dysfunction and cell death. Am J Physiol Heart Circ Physiol, published ahead of print October 28, 2011, doi: 10.1152/ajpheart.00833.2011.

SIRT3 and cardiac mitochondria

khkeehan — Thu, 17 Nov 2011 18:41:27 +0000

Post-translational modification through acetylation by the NAD+-dependent deacetylase sirtuin-3, or SIRT3, has recently emerged as a key player in regulating mitochondrial function. What is SIRT3 doing in cardiac mitochondria? How does it impact cardiac physiology and pathophysiology? Listen as Editor in Chief William Stanley and Associate Editor Junichi Sadoshima talk with the author Michael Sack (National Heart, Lung and Blood Institute, NIH) about his just-published Review article which tackles these very questions.

Michael N. Sack. Emerging characterization of the role of SIRT3 mediated mitochondrial protein deacetylation in the heart. Am J Physiol Heart Circ Physiol, published ahead of print October 7, 2011, doi:10.1152/ajpheart.00199.2011.

Electrophysiology of hiPSC-derived cardiomyocytes

khkeehan — Wed, 09 Nov 2011 14:01:06 +0000

The discovery of induced pluripotent stem (iPS) cells has allowed researchers to generate human cardiomyocytes from patients. Why is this important? Human iPS cells are useful for studying normal and diseased human cardiomyocytes and for discovering new drug therapies to treat cardiovascular disease. Until now, methods for generating cardiomyocytes from human iPS or ES cells were inconsistent and often unreliable. The recent article by Ma et al presents a new method to obtain a large quantity of cultured cardiac myocytes using embryoid body formation and blasticidin selection techniques resulting in more than 98% purity from human iPS cell lines. Associate Editor Junichi Sadoshima talks with authors Craig January (University of Wisconsin – Madison) and Brad Swanson (Cellular Dynamics International), along with leading expert Diego Fraidenraich (University of Medicine and Dentistry, New Jersey), about this groundbreaking research and its many potential applications.

Junyi Ma, Liang Guo, Steve J Fiene, Blake D Anson, James A Thomson, Timothy J. Kamp, Kyle L Kolaja, Bradley J Swanson, and Craig T. January. High Purity Human Induced Pluripotent Stem Cell (hiPSC) Derived Cardiomyocytes: Electrophysiological Properties of Action Potentials and Ionic Currents. Am J Physiol Heart Circ Physiol, published ahead of print September 2, 2011, doi:10.1152/ajpheart.00694.2011.

Carotid baroreflex responsiveness is impaired in normotensive African American men

khkeehan — Thu, 03 Nov 2011 15:46:17 +0000

It almost goes without saying that human beings are genetically diverse and that diseases develop differently, and at different rates, across various racial groups in the human population. Case in point: African Americans are predisposed to developing far deadlier forms of hypertension earlier in life than other racial group counterparts. Associate Editor Irving Zucker talks with lead author David Keller (University of Texas Arlington) and expert Peter Raven (University of North Texas Health Science Center) about the work of Holwerda et al, which studied the possibility of the baroreflex contributing to the development of hypertension in African American males.

Seth W. Holwerda, Diana Fulton, Wendy L. Eubank, and David M. Keller. Carotid Baroreflex Responsiveness is Impaired in Normotensive African American Men. Am J Physiol Heart Circ Physiol, October 2011 301:H1639-H1645; published ahead of print August 12, 2011, doi:10.1152/ajpheart.00604.2011.

Shedding of the Glycocalyx and Capillary Hemodynamics

khkeehan — Thu, 20 Oct 2011 14:48:15 +0000

We know that the endothelial surface is coated with glycocalyx. But why should we be concerned about the effects of shedding the glycocalyx on microvascular hemodynamics? Editor in Chief William C. Stanley talks with senior author Herbert Lipowsky (Pennsylvania State University) and leading expert Jos A. Spaan (University of Amsterdam) about the unique model presented in the article by Lipowsky et al that mimics aspects of acute vascular inflammation and investigates how shedding of the glycocalyx impacts many pathologies including diabetes.

Herbert H. Lipowsky, Lujia Gao, and Anne Lescanic. Shedding of the Endothelial Glycocalyx in Arterioles, Capillaries and Venules and its Effect on Capillary Hemodynamics During Inflammation. Am J Physiol Heart Circ Physiol, published ahead of print September 16, 2011, doi:10.1152/ajpheart.00803.2011.

DHEA inhibits the Src/STAT3 constitutive activation

khkeehan — Tue, 04 Oct 2011 18:35:35 +0000

Pulmonary hypertension affects millions of patients with increasing prevalence each year, and clinical treatments are still in their infancy. In our latest podcast, Associate Editor Leon de Windt talks with senior author Sebastien Bonnet (Universite Laval) and leading expert Laura Gonzalez Bosc (University of New Mexico) about the article by Paulin et al, which reports the first demonstration of DHEA blocking two major transcription factors—STAT3 and NFAT. Is DHEA, a commercially available natural steroid hormone and antioxidant, the newest entry point for pharmacological intervention and treatment of pulmonary hypertension? Listen in and find out.

Roxane Paulin, Jolyane Meloche, Maria Helena Jacob, Malik Bisserier, Audrey Courboulin, and Sebastien Bonnet. Dehydroepiandrosterone inhibits the Src/STAT3 constitutive activation in pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol, published ahead of print September 2, 2011, doi:10.1152/ajpheart.00654.2011.

Alignment of SR-mitochondrial junctions and contact points

khkeehan — Wed, 28 Sep 2011 14:55:06 +0000

In our latest podcast we explore the connections between the sarcoplasmic reticulum and the mitochondria within calcium regulation during signaling contractile function and regulation of mitochondrial metabolism. Associate Editor Gary Lopaschuk interviews senior author Gyorgy Csordas (Thomas Jefferson University) and leading expert Pal Pacher (National Institutes of Health), seeking to explore a central question in the work by Garcia-Perez et al—how are the SR and the mitochondria communicating with each other?

Cecilia Garcia-Perez, Timothy G. Schneider, Gyorgy Hajnoczky, and Gyorgy Csordas. Alignment of sarcoplasmic reticulum-mitochondrial junctions with mitochondrial contact points. Am J Physiol Heart Circ Physiol, published online ahead of print August 19, 2011, doi:10.1152/ajpheart.00397.2011.