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...

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Published in:Journal of molecular and cellular cardiology 2011-06, Vol.50 (6), p.1017-1025
Main Authors: van Deel, Elza D, de Boer, Martine, Kuster, Diederik W, Boontje, Nicky M, Holemans, Patricia, Sipido, Karin R, van der Velden, Jolanda, Duncker, Dirk J
Format: Article
Language:English
Subjects:
Actin Cytoskeleton - metabolism
Animals
Aortic stenosis
Aortic Valve Stenosis - complications
Aortic Valve Stenosis - mortality
Aortic Valve Stenosis - physiopathology
Calcium-Binding Proteins - metabolism
Cardiac dysfunction
Cardiovascular
Exercise
Female
Genetic Markers - genetics
Homeodomain Proteins - metabolism
Hypertrophy
Hypertrophy, Left Ventricular - etiology
Hypertrophy, Left Ventricular - mortality
Hypertrophy, Left Ventricular - physiopathology
Male
Mice
Mice, Inbred C57BL
Myofilament function
Physical Conditioning, Animal
Pressure-overload
Ryanodine Receptor Calcium Release Channel - metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism
Survival Analysis
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Summary: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 Ca2+ -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 Ca2+ -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.
ISSN:0022-2828
1095-8584
DOI:10.1016/j.yjmcc.2011.01.016