title: Exercise training does not improve cardiac function in compensated or decompensated left ventricular hypertrophy induced by aortic stenosis.
abstract: There is ample evidence that regular exercise exerts beneficial effects on left ventricular (LV) hypertrophy, remodeling and dysfunction produced by ischemic heart disease or systemic hypertension. In contrast, the effects of exercise on pathological LV hypertrophy and dysfunction produced by LV outflow obstruction have not been studied to date. Consequently, we evaluated the effects of 8 weeks of voluntary wheel running in mice (which mitigates post-infarct LV dysfunction) on LV hypertrophy and dysfunction produced by mild (mTAC) and severe (sTAC) transverse aortic constriction. mTAC produced ~40% LV hypertrophy and increased myocardial expression of hypertrophy marker genes but did not affect LV function, SERCA2a protein levels, apoptosis or capillary density. Exercise had no effect on global LV hypertrophy and function in mTAC but increased interstitial collagen, and ANP expression. sTAC produced ~80% LV hypertrophy and further increased ANP expression and interstitial fibrosis and, in contrast with mTAC, also produced LV dilation, systolic as well as diastolic dysfunction, pulmonary congestion, apoptosis and capillary rarefaction and decreased SERCA2a and ryanodine receptor (RyR) protein levels. LV diastolic dysfunction was likely aggravated by elevated passive isometric force and Ca(2+)-sensitivity of myofilaments. Exercise training failed to mitigate the sTAC-induced LV hypertrophy and capillary rarefaction or the decreases in SERCA2a and RyR. Exercise attenuated the sTAC-induced increase in passive isometric force but did not affect myofilament Ca(2+)-sensitivity and tended to aggravate interstitial fibrosis. In conclusion, exercise had no effect on LV function in compensated and decompensated cardiac hypertrophy produced by LV outflow obstruction, suggesting that the effect of exercise on pathologic LV hypertrophy and dysfunction depends critically on the underlying cause.
authors.affiliation: Experimental Cardiology, Thoraxcenter, Cardiovascular Research School COEUR, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Elza D
authors.initials: ED
authors.lastname: van Deel
authors.forename: Martine
authors.initials: M
authors.lastname: de Boer
authors.forename: Diederik W
authors.initials: DW
authors.lastname: Kuster
authors.forename: Nicky M
authors.initials: NM
authors.lastname: Boontje
authors.forename: Patricia
authors.initials: P
authors.lastname: Holemans
authors.forename: Karin R
authors.initials: KR
authors.lastname: Sipido
authors.forename: Jolanda
authors.initials: J
authors.lastname: van der Velden
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications* / Q000401:mortality / Q000503:physiopathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010805:Physical Conditioning, Animal; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D016019:Survival Analysis; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D005819:Genetic Markers; D018398:Homeodomain Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C107836:Tlx2 protein, mouse