Published online before print January 26, 2006, doi: 10.1161/01.RES.0000205766.97556.00
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© 2006 American Heart Association, Inc.
Integrative Physiology |
Exercise Can Prevent and Reverse the Severity of Hypertrophic Cardiomyopathy
From the Department of Molecular, Cellular, and Developmental Biology (J.P.K., A.M., D.M.B., T.H., S.W.L., L.A.L.), University of Colorado, Boulder; Division of Endocrinology, Metabolism, and Diabetes (P.A.W.), Department of Medicine, University of Colorado Health Sciences Center, Aurora; Division of Cardiology (B.L.S.), Department of Medicine UCHSC and Denver Health Medical Center; Departments of Internal Medicine and Pharmacology (P.R.), Duke University Medical School, Durham, NC.
Correspondence to Leslie A. Leinwand, PhD, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Campus Box 347, Boulder, CO 80309-0347. E-mail Leslie.leinwand{at}colorado.edu
Hypertrophic cardiomyopathy (HCM) is the most common form of sudden death in young competitive athletes. However, exercise has also been shown to be beneficial in the setting of other cardiac diseases. We examined the ability of voluntary exercise to prevent or reverse the phenotypes of a murine model of HCM harboring a mutant myosin heavy chain (MyHC). No differences in voluntary cage wheel performance between nontransgenic (NTG) and HCM male mice were seen. Exercise prevented fibrosis, myocyte disarray, and induction of "hypertrophic" markers including NFAT activity when initiated before established HCM pathology. If initiated in older HCM animals with documented disease, exercise reversed myocyte disarray (but not fibrosis) and "hypertrophic" marker induction. In addition, exercise returned the increased levels of phosphorylated GSK-3ß to those of NTG and decreased levels of phosphorylated CREB in HCM mice to normal levels. Exercise in HCM mice also favorably impacted components of the apoptotic signaling pathway, including Bcl-2 (an inhibitor of apoptosis) and procaspase-9 (an effector of apoptosis) expression, and caspase-3 activity. Remarkably, there were no differences in mortality between exercised NTG and HCM mice. Thus, not only was exercise not harmful but also it was able to prevent and even reverse established cardiac disease phenotypes in this HCM model.
Key Words: apoptosis • exercise • hypertrophic cardiomyopathy • remodeling
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Circ. Res. 2006 98: 443-445.
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