Exercise training in genetic models of heart failure: Mice with congenital disruption of the muscle LIM protein (MLP) or inducible cardiomyocyte-specific disruption of the sarco-(endo)plasmic reticulum Ca2+ ATPase (SERCA2)

Abstract

Several lines of evidence suggest that exercise training improves cardiac function and enhances aerobic performance after myocardial infarction, but it is not known whether similar beneficial effects occur in heart failure secondary to genetic aberrations. The present thesis addresses cellular and molecular changes in global heart failure after genetic interventions; the relation to global cardiac function and the response to exercise training. Our working hypothesis was that exercise training would delay the progressive deterioration in cardiac function in two models of genetically established heart failure. These assumptions were based on a body of evidence that exercise training improves cardiac contractility and calcium handling in healthy hearts and after myocardial infarction.

Main results There is a close correlation between a functional SERCA2 protein and the ability to increase or maintain VO2max.Maintenance of cardiac output is dependent on mechanisms that seem to be partly independent of SERCA2 abundance.Training improves cardiac function in both MLP and SERCA2 deficient mice, compared to their sedentary counterparts.Despite reduced or a smaller improvement in VO2max, maximal running speed was maintained or improved in exercise-training mice with heart failure, secondary to MLP deficiency or SERCA2 disruption.