title: Exercise can prevent and reverse the severity of hypertrophic cardiomyopathy.
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-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.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Konhilas
authors.forename: Peter A
authors.initials: PA
authors.lastname: Watson
authors.forename: Alexander
authors.initials: A
authors.lastname: Maass
authors.forename: Dana M
authors.initials: DM
authors.lastname: Boucek
authors.forename: Todd
authors.initials: T
authors.lastname: Horn
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Luckey
authors.forename: Paul
authors.initials: P
authors.lastname: Rosenberg
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Leinwand
mesh_terms: D000818:Animals; D017209:Apoptosis; D002312:Cardiomyopathy, Hypertrophic / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005355:Fibrosis; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D064326:MEF2 Transcription Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D018006:Myogenic Regulatory Factors / Q000032:analysis; D018995:Myosin Heavy Chains / Q000235:genetics; D050778:NFATC Transcription Factors / Q000032:analysis; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D018006:Myogenic Regulatory Factors; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D018995:Myosin Heavy Chains