Exercise Training Enhances Myocardial Mitophagy and Improves Cardiac Function via Irisin/FNDC5-PINK1/Parkin Pathway in MI Mice

Abstract

Myocardial infarction is the major cause of death in cardiovascular disease. In vitro and in vivo models are used to find the exercise mode which has the most significant effect on myocardial irisin/FNDC5 expression and illuminate the cardioprotective role and mechanisms of exercise-activated myocardial irisin/FNDC5-PINK1/Parkin-mediated mitophagy in myocardial infarction. The results indicated that expression of irisin/FNDC5 in myocardium could be up-regulated by different types of exercise and skeletal muscle electrical stimulation, which then promotes mitophagy and improves cardiac function and the effect of resistance exercise. Resistance exercise can improve cardiac function by activating the irisin/FNDC5-PINK1/Parkin-LC3/P62 pathway, regulating mitophagy and inhibiting oxidative stress. OPA1 may play an important role in the improvement of cardiac function and mitophagy pathway in myocardial infarction mice by irisin-mediated resistance exercise. Resistance exercise is expected to become an effective therapeutic way to promote myocardial infarction rehabilitation.

Exercise training improves cardiac function and regulates myocardial mitophagy differently in ischaemic and pressure‐overload heart failure mice

“…However, the effects of different aerobic exercise modalities on cardiac mitophagy and cardiac function are significantly different and highly controversial (Chang & Ma, 2017). Our findings confirmed that both MICT and HIIT improved autophagic flux and mitophagy levels in mice with ischaemic and pressure‐overload HF, which was partially consistent with previous lesser evidence (Chang & Ma, 2017; Li et al., 2021; Ma et al., 2021; Moradi et al., 2019; Zhao et al., 2018). Note too that exercise‐induced mitophagy may differ from the conventional pathways, and studies have shown that PRKN played an indispensable role in exercise‐induced mitophagy initiation (Drake et al., 2019; Eiyama & Okamoto, 2015; Ni et al., 2015; Wu et al., 2019).…”

“…In addition, HIF1α in the myocardium of mice with both aetiologies of HF was also significantly reduced in the present study, which was consistent with the decreased HIF1α in the (Chang & Ma, 2017). Our findings confirmed that both MICT and HIIT improved autophagic flux and mitophagy levels in mice with ischaemic and pressure-overload HF, which was partially consistent with previous lesser evidence (Chang & Ma, 2017;Li et al, 2021;Ma et al, 2021;Moradi et al, 2019;Zhao et al, 2018).…”

“…Exercise can affect cardiac function by altering myocardial mitophagy levels. For example, Li and colleagues (2021) demonstrated that different types of exercise promoted myocardial mitophagy and improved cardiac function in healthy mice, and resistance exercise optimized MI‐mouse cardiac function by activating irisin/fibronectin type III domain‐containing protein 5 (FNDC5)–PINK1/PRKN‐mediated mitophagy. Ma and colleagues (2021) also found MICT could ameliorate autophagy of myocardial mitochondria.…”

Establishing Equivalent Aerobic Exercise Parameters Between Early-Stage Parkinson’s Disease and Pink1 Knockout Rats

“…It is possible that the parameters of the exercise paradigm used in this study were not rigorous enough to exacerbate similar cardiovascular changes in PinK1 KO rats. There also is evidence that augmented mitochondrial function plays a role in exercise-related changes in mitophagy in cardiac tissue [73,74]…”

Irisin is an Effector Molecule in Exercise Rehabilitation Following Myocardial Infarction (Review)

“…Exercise is the main inducer of irisin secretion both in healthy and dysregulated metabolism individuals ( Huh et al, 2015 ). Studies have confirmed that exercise-induced irisin is correlated with improvement of cardiac function in general ( Seo et al, 2020 ), which partly by modulating autophagy and mitochondrial function ( Li et al, 2021a ; He et al, 2021 ). Further previous animal studies report that irisin is implicated in cerebrovascular protective effects of exercise by alleviating ischemic neuron injury ( Li et al, 2017 ; Lourenco et al, 2019 ).…”