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

Hangzhuo Li,Yue Xi,Qiaoqin Liang,Mengxin Cai,Wenyan Bo,Zhenjun Tian,Shuguang Qin

doi:10.3390/biomedicines9060701

Hangzhuo Li, Yue Xi + Show 5 more

Open Access

https://doi.org/10.3390/biomedicines9060701

Copy DOI

Journal: Biomedicines	Publication Date: Jun 21, 2021
Citations: 26	License type: CC BY 4.0

Affiliation: Shaanxi Normal University

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.

Highlights

Myocardial infarction (MI) is a major cause of death in cardiovascular diseases [1].During MI, the level of local myocardial oxidative stress elevated abnormally due to ischemia and hypoxia, resulting in the death of a large number of cardiomyocytes, myocardial fibrosis and eventually heart failure [2]
The MI model was established by permanent ligation of the left anterior descending coronary artery (LAD) of the heart. (The preparation procedure of myocardial infarction model is as follows: Mice were anesthetized with isoflurane, the limbs were fixed on an operating table after skin preparation, the chest was opened and the heart was squeezed, and ligation was performed 1–2 mm below the left anterior descending coronary artery)
Resistance exercise significantly inincreased MI myocardial irisin/FNDC5 and OPA1 expression, enhanced PINK1/Parkin creased MI myocardial irisin/FNDC5 and OPA1 expression, enhanced PINK1/Parkin pathway mitophagy, alleviated oxidative stress and improved MI cardiac function. These pathway mitophagy, alleviated oxidative stress and improved MI cardiac function. These results suggested that resistance exercise inhibited oxidative stress and improved cardiac results suggested that resistance exercise inhibited oxidative stress and improved cardiac function in MI, partially via activating FNDC5/Irisin-PINK1/Pakin-LC3II/I-P62 signaling function in MI, partially via activating FNDC5/Irisin-PINK1/Pakin-LC3II/I-P62 signaling pathway

Summary

Introduction

Myocardial infarction (MI) is a major cause of death in cardiovascular diseases [1].During MI, the level of local myocardial oxidative stress elevated abnormally due to ischemia and hypoxia, resulting in the death of a large number of cardiomyocytes, myocardial fibrosis and eventually heart failure [2]. Irisin is a secreted peptide proteolytically processed from transmembrane protein fibronectin type III domain protein 5 (FNDC5) [8]. It was originally found in mice and human serum and can be secreted in skeletal muscle, myocardium, adipose and other tissues [9]. Hypoxia and abnormal energy metabolism as well as impaired cardiac function, mitophagy could improve cardiac function by removing damaged mitochondria [11]. Exercise-activated mitophagy was mediated by the irisin/FNDC5-PINK1/Parkin-LC3/P62 pathway, which could significantly increase the level of myocardial anti-oxidation and improve cardiac function [13].

Objectives

Methods

Results

Conclusion