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Exercise can prevent and reverse the severity of hypertrophic cardiomyopathy
Exercise can prevent and reverse the severity of hypertrophic cardiomyopathy.
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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-3beta 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.
Konhilas JP, Watson PA, Maass A, Boucek DM, Horn T, Stauffer BL, Luckey SW, Rosenberg P, Leinwand LA
Circulation research
2006-03-03 00:00
98
4
540-8
Animals,Apoptosis,Cardiomyopathy, Hypertrophic,Caspase 3,Caspases,Cyclic AMP Response Element-Binding Protein,Fibrosis,Glycogen Synthase Kinase 3,Male,Mice,Mice, Inbred C57BL,Myocardium,Myogenic Regulatory Factors,Myosin Heavy Chains,NFATC Transcription Factors,Phosphorylation,Physical Conditioning, Animal,RNA, Messenger,Signal Transduction,Creb1 protein, mouse,Cyclic AMP Response Element-Binding Protein,Mef2a protein, mouse,Myogenic Regulatory Factors,Myosin Heavy Chains,NFATC Transcription Factors,RNA, Messenger,Glycogen Synthase Kinase 3,glycogen synthase kinase 3 beta,Casp3 protein, mouse,Caspase 3,Caspases
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA
Circ. Res.
NHLBI F32 HL 67543, NHLBI F32 HL 70509, NHLBI F32 HL 72565, NHLBI HL 56510
1524-4571
10.1161/01.RES.0000205766.97556.00
01.RES.0000205766.97556.00
711
True
16439687
