Postinfarction exercise training alleviates cardiac dysfunction and adverse remodeling via mitochondrial biogenesis and SIRT1/PGC‐1α/PI3K/Akt signaling

Abstract

Exercise training mitigates cardiac pathological remodeling and dysfunction caused by myocardial infarction (MI), but its underlying cellular and molecular mechanisms remain elusive. Our present study in an in vivo rat model of MI determined the impact of post-MI exercise training on myocardial fibrosis, mitochondrial biogenesis, antioxidant capacity, and ventricular function. Adult male rats were randomized into: (a) Sedentary control group; (b) 4-week treadmill exercise training group; (c) Sham surgery group; (d) MI group with permanent ligation of left anterior descending coronary artery and kept sedentary during post-MI period; and (e) post-MI 4-week exercise training group. Results indicated that exercise training significantly improved post-MI left ventricular function and reduced markers of cardiac fibrosis. Exercise training also significantly attenuated MI-induced mitochondrial damage and oxidative stress, which were associated with enhanced antioxidant enzyme expression and/or activity and total antioxidant capacity in the heart. Interestingly, the adaptive activation of the SIRT1/ PGC-1α/PI3K/Akt signaling following MI was further enhanced by post-MI exercise training, which is likely responsible for exercise-induced cardioprotection and mitochondrial biogenesis. In conclusion, this study has provided novel evidence on the activation of SIRT1/PGC-1α/PI3K/Akt pathway, which may mediate exerciseinduced cardioprotection through reduction of cardiac fibrosis and oxidative stress, as well as improvement of mitochondrial integrity and biogenesis in post-MI myocardium.

HIF‐1α‐induced up‐regulation of microRNA‐126 contributes to the effectiveness of exercise training on myocardial angiogenesis in myocardial infarction rats

“…Many factors contribute to the beneficial effects of exercise in maintaining cardiovascular system health and delaying the progress of heart diseases 24 . The beneficial effects of exercise may be associated with anabolic/catabolic balance, calcium handling and myocardial fibrosis 25‐27 . Recently, myocardial angiogenesis has been recognized as one of the innovative therapeutic methods for the treatment of MI 28 .…”

Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction

“…All in vivo animal experiments were conducted in the Laboratory of Exercise and Cardiovascular Health, Institute of Sports and Exercise Biology, Shaanxi Normal University. The rat model of MI was established by permanent ligation of the left anterior descending coronary artery (LAD) of the heart as previously described [ 62 , 63 ]. In brief, the rat was anaesthetized with sodium pentobarbital (30 mg/kg, i.p.)…”

Exercise Training Stabilizes RyR2-Dependent Ca2+ Release in Post-infarction Heart Failure

“…This limits the potential for extrapolation to propensity for arrhythmias in vivo. However, other mechanisms are also important for antiarrhythmic effects of ET, such as alterations in repolarization reserve (38) or reductions in fibrosis levels (44), although the latter is debated after findings in healthy rats (45). As these other mechanisms were not the focus of our study, we would not have been able to ascertain a causal link between the cellular phenomena and arrhythmias regardless of any observed effects on arrhythmias.…”