Voluntary exercise in a murine model of hypertrophic cardiomyopathy prevented and reversed established cardiac disease phenotypes, including myocyte disarray, without increasing mortality.
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.
Konhilas et al. (Fri,) conducted a other in Hypertrophic cardiomyopathy. Voluntary exercise (cage wheel) vs. Nontransgenic mice and non-exercised HCM mice was evaluated on Cardiac disease phenotypes (fibrosis, myocyte disarray, hypertrophic markers, mortality). Voluntary exercise in a murine model of hypertrophic cardiomyopathy prevented and reversed established cardiac disease phenotypes, including myocyte disarray, without increasing mortality.