FSTL1 as a Potential Mediator of Exercise-Induced Cardioprotection in Post-Myocardial Infarction Rats.

Exercise training has been reported to ameliorate heart dysfunction in both humans and animals after myocardial infarction (MI), but the underlying mechanisms are poorly understood. Follistatin-like1 (FSTL1) is a cardioprotective factor against ischemic injury and is induced in cardiomyocytes and skeletal muscle in ischemic and hypoxic conditions. To test the hypothesis that FSTL1 may be a molecular link between exercise and improved heart function post MI, we subjected MI-rats, induced by left coronary artery ligation, to two modes of exercise: intermittent aerobic exercise (IAE) or mechanical vibration training (MVT), for four weeks and examined the relevance of FSTL1 to exercise-mediated cardiac effects. Exercise improved the functional performance, reduced fibrosis of MI-hearts and induced FSTL1 expression, the TGFβ-Smad2/3 signaling and angiogenesis in myocardium. In gastrocnemius, exercise increased the cross-sectional area of myocytes and FSTL1 expression. Importantly, exercise increased circulating FSTL1 levels, which were positively correlated with the skeletal muscle FSTL1 expression and negatively correlated with heart fibrosis. Overall, the IAE was more effective than that of MVT in cardioprotection. Finally, exogenous FSTL1 administration directly improved angiogenesis as well as functionality of post-MI hearts. Taken together, we have demonstrated that FSTL1 is a potential mediator of exercise-induced cardioprotection in post-MI rats.