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

Abstract

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.

TPPU enhanced exercise‐induced epoxyeicosatrienoic acid concentrations to exert cardioprotection in mice after myocardial infarction

“…Although a growing number of studies have focused on the function of EETs and the related metabolites, we are the first to illustrate the relationship between exercise and EETs. As reported previously, exercise induces many mediators that exert important cardioprotective functions . Similarly, EETs are induced by exercise and may also be an exercise‐induced mediator for exerting cardioprotective properties after MI.…”

Novel Mechanisms of Exercise-Induced Cardioprotective Factors in Myocardial Infarction

“…Exercise training has been shown to induce FSTL1 expression (Xi et al, 2016;Kon et al, 2019a). In healthy individuals, 60 min of cycling dramatically increased the serum FSTL1 level by 22%, with a concentration increase from 16.9 ng/mL (pre-exercise) to 20.1 ng/mL (immediately after exercise), which further increased to 21.9 ng/mL at 30 min after completing the exercise [23].…”

“…More interestingly, exercise training further increases ischemiainduced FSTL1 expression. A previous study showed that FSTL1 expression in MI mice was 1.96-fold higher than that in control mice, and it further increased by 4.04-fold after intermittent aerobic exercise (Xi et al, 2016). In addition, exercise-induced FSTL1 has been shown to improve cardiac remodeling and prognosis after MI via promoting angiogenesis and reducing cardiac fibrosis (Xi et al, 2016).…”

Module analysis captures pancancer genetically and epigenetically deregulated cancer driver genes for smoking and antiviral response

“…The most common cancer driver gene, FSTL1, regulates 8 of the 43 enriched modules, representing a potential cancer driver gene that regulates angiogenesis. This gene has been shown to be involved in proliferation, migration and invasion [34][35][36] and was recently linked with angiogenesis in postmyocardial infarction rats 37 . Twelve modules are enriched in epithelial-to-mesenchymal transition (EMT) pathways.…”