Abstract
Aerobic exercise mitigates oxidative stress and apoptosis caused by myocardial infarction (MI) even though the precise mechanisms remain completely elusive. In this study, we investigated the potential mechanisms of aerobic exercise in ameliorating the cardiac function of mice with MI. In vivo, MI was induced by left anterior descending (LAD) coronary artery ligation in wild-type mice, alcat1 knockout, and fgf21 knockout mice. The mice were exercised under a moderate-intensity protocol for 6 weeks at one week later post-MI. In vitro, H9C2 cells were treated with lentiviral vector carrying alcat1 gene, recombinant human FGF21 (rhFGF21), PI3K inhibitor, and H2O2 to explore the potential mechanisms. Our results showed that aerobic exercise significantly increased the FGF21 expression and decreased the ALCAT1 expression in the hearts of mice with MI. fgf21 knockout weakened the inhibitory effects of aerobic exercise on oxidative stress, endoplasmic reticulum (ER) stress, and apoptosis in mice with MI. Both/either alcat1 knockout and/or aerobic exercise improved cardiac function by inhibiting oxidative stress and apoptosis in the MI heart. rhFGF21 inhibited both H2O2 and overexpression of ALCAT1-induced oxidative stress and apoptosis by activating the PI3K/AKT pathway in H9C2 cells. In conclusion, our results showed that aerobic exercise alleviated oxidative stress and apoptosis by activating the FGF21/FGFR1/PI3K/AKT pathway or inhibiting the hyperexpression of ALCAT1, which ultimately improved the cardiac function in MI mice.
Highlights
Heart failure (HF) is a major public health problem threatening the health and safety of over 23 million people worldwide
We found that the improvement of myocardial function by exercise was related to the expression of Fibroblast growth factor 21 (FGF21)
Compared with the ME group in WT mice, the inhibitory effect of exercise on excessive proliferation of myocardial collagen fibers of ME group in the fgf21-/- mice was weakened (p < 0:01, Figures 1(a) and 1(b)). It indicates that the repression of FGF21 expression inhibited the alleviating effect of partial aerobic exercise on the morphological changes after Myocardial infarction (MI)
Summary
Heart failure (HF) is a major public health problem threatening the health and safety of over 23 million people worldwide. Fibroblast growth factor 21 (FGF21), as an endocrine factor, is a unique member of the FGF superfamily and belongs to the subgroup of fibroblast growth factor 19 It is involved in the regulation of metabolic process and has the effects of antioxidative stress and apoptosis [3,4,5,6], antiinflammatory, and promotion of angiogenesis [6, 7]. Animal experiments have found that the level of serum FGF21 increased significantly after a single acute exercise in mice [12]. These indicate that FGF21 might play an organ protective role as “exerkines.” little is known about whether FGF21 mediates
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