Exercise can prevent and reverse the severity of hypertrophic cardiomyopathy

John Konhilas, Peter A. Watson, Alexander Maass, Dana M. Boucek, Todd Horn, Brian L. Stauffer, Stephen W. Luckey, Paul Rosenberg, Leslie A. Leinwand

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

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-3β 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.

Original languageEnglish (US)
Pages (from-to)540-548
Number of pages9
JournalCirculation Research
Volume98
Issue number4
DOIs
StatePublished - Mar 2006
Externally publishedYes

Fingerprint

Hypertrophic Cardiomyopathy
Exercise
Muscle Cells
Heart Diseases
Fibrosis
Apoptosis
Glycogen Synthase Kinase 3
Phenotype
Myosin Heavy Chains
Caspase 9
Sudden Death
Caspase 3
Athletes
Pathology
Mortality

Keywords

  • Apoptosis
  • Exercise
  • Hypertrophic cardiomyopathy
  • Remodeling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Konhilas, J., Watson, P. A., Maass, A., Boucek, D. M., Horn, T., Stauffer, B. L., ... Leinwand, L. A. (2006). Exercise can prevent and reverse the severity of hypertrophic cardiomyopathy. Circulation Research, 98(4), 540-548. https://doi.org/10.1161/01.RES.0000205766.97556.00

Exercise can prevent and reverse the severity of hypertrophic cardiomyopathy. / Konhilas, John; Watson, Peter A.; Maass, Alexander; Boucek, Dana M.; Horn, Todd; Stauffer, Brian L.; Luckey, Stephen W.; Rosenberg, Paul; Leinwand, Leslie A.

In: Circulation Research, Vol. 98, No. 4, 03.2006, p. 540-548.

Research output: Contribution to journalArticle

Konhilas, J, Watson, PA, Maass, A, Boucek, DM, Horn, T, Stauffer, BL, Luckey, SW, Rosenberg, P & Leinwand, LA 2006, 'Exercise can prevent and reverse the severity of hypertrophic cardiomyopathy', Circulation Research, vol. 98, no. 4, pp. 540-548. https://doi.org/10.1161/01.RES.0000205766.97556.00
Konhilas, John ; Watson, Peter A. ; Maass, Alexander ; Boucek, Dana M. ; Horn, Todd ; Stauffer, Brian L. ; Luckey, Stephen W. ; Rosenberg, Paul ; Leinwand, Leslie A. / Exercise can prevent and reverse the severity of hypertrophic cardiomyopathy. In: Circulation Research. 2006 ; Vol. 98, No. 4. pp. 540-548.
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