Protective effects of mitochondrial transplantation on myocardial ischemia/reperfusion injury and its impact on macrophages
WANG Xinyi
LIU Zhiyuan
SUN Fangfang
ZHANG Fuyang
TAO Ling
Abstract：Objective To determine the protective effects of mitochondrial transplantation on myocardial ischemia/reperfusion(MI/R)injury and explore its impact on macrophages.Methods C57BL/6J mice underwent MI/R surgery via ligation of the left anterior descending coronary artery or a sham operation(Sham).Prior to reperfusion,mice were randomly administered an intramyocardial injection of either Vehicle or mitochondria isolated from C57BL/6J neonatal cardiomyocytes.Cardiac function was assessed using echocardiography,and myocardial apoptosis was evaluated with TUNEL staining at 1 d post-surgery.Cardiac function and myocardial fibrosis were further assessed at 28 d post-surgery using echocardiography and Masson's trichrome staining,respectively.Mitochondria of C57BL/6J neonatal rat cardiomyocytes were isolated with DsRed signal labeled via adenovirus and transplanted into the myocardium of MI/R mice at the time of reperfusion.The abundance of DsRed-labeled exogenous mitochondria in cardiomyocytes,macrophages,and vascular endothelial cells was detected at 1,6,and 12 h post-transplantation.Peritoneal macrophages from C57BL/6J mice were isolated,activated with lipopolysaccharides(LPS)to induce a pro-inflammatory state,and then treated with DsRed-labeled exogenous mitochondria to observe the colonization of transplanted mitochondria in macrophages and the impact on inflammatory gene expression in macrophages.Macrophages were depleted using clodronate liposomes,followed by Sham or MI/R surgery in C57BL/6J mice,and an intramyocardial injection of either Vehicle or exogenous mitochondria at reperfusion.Echocardiography and TUNEL staining were used to assess cardiac function and myocardial apoptosis at 1 d post-surgery,with further evaluation on 28 d for cardiac function and myocardial fibrosis by echocardiography and Masson's trichrome staining,respectively.Results Mitochondrial transplantation significantly alleviated MI/R injury(P＜0.01).The transplanted mitochondria were primarily taken up by macrophages(P＜0.01),and inhibited the expression of inflammatory genes in LPS-stimulated pro-inflammatory macrophages(P＜0.01).Macrophage depletion significantly weakened the protective effects of mitochondrial transplantation on MI/R injury(P＜0.01).Conclusion Mitochondrial transplantation may exert its protective effects against MI/R injury by modulating macrophage function.
Keywords：mitochondrial transplantationmyocardial ischemia/reperfusion injurymacrophages
Publication Date：2025-02-27
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 153-159 )