Bone marrow mesenchymal stem cells-derived exosomes play a protective role in myocardial infarction in mice through microRNA-210

SHEN Yibo; LI Congye; ZHENG Nanbo; WU Guanji; HAO Yuanyuan

doi:10.13276/j.issn.2097-1656.2025.02.007

Abstract：Objective To investigate the role of microRNA-210,a bioactive substance of exosomes(exos)derived from bone marrow mesenchymal stem cells(BMSCs),in mice after myocardial infarction(MI)to evaluate its potential clinical value in MI.Methods BMSCs-exos were extracted,identified and analyzed by electron microscopy and Western blotting.All mice were randomly divided into four groups:Sham group(only thoracotomy without ligation),MI group(thoracotomy and left anterior descending artery ligation),MI+BMSCs-exos group(left anterior descending artery ligation followed by injection of BMSCs-exos),MI+BMSCs-exos+microRNA-210 inhibitor group(left anterior descending artery ligation followed by injection of BMSCs-exos transfected with microRNA-210 inhibitor).After the mouse model of MI was established by left anterior descending coronary artery ligation,exos or exos transfected with microRNA-210 inhibitor were infused intramuscularly around the infarcted myocardium immediately.MicroRNA-210 was extracted from myocardial tissues of each group and its expression was detected by PCR.The cardiac function was tested by echocardiography.The MI area was measured after Evans blue staining of the heart.The apoptosis of cardiomyocytes in each group was detected by TUNEL.The expression of apoptosis-related proteins in cardiomyocytes was detected by Western blotting.Results Compared with Sham group,left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in MI group were significantly decreased,the MI area was significantly increased,the apoptosis level of cardiomyocytes was significantly increased,the apoptosis-related protein Bcl-2 expression was significantly decreased,and Bax expression was significantly increased(P＜0.05).Compared with MI group,LVEF and LVFS in MI+BMSCs-exos group were significantly increased,MI area was significantly decreased,myocardial apoptosis level was significantly decreased,apoptosis-related protein Bcl-2 expression was significantly increased,and Bax expression was significantly decreased(P＜0.05).Compared with MI+BMSCs-exos group,LVEF and LVFS in MI+BMSCs-exos+microRNA-210 inhibitor group were significantly decreased,MI area was significantly increased,myocardial apoptosis level was significantly increased,apoptosis-related protein Bcl-2 expression was significantly decreased,and Bax expression was significantly increased(P＜0.05).Conclusion BMSCs-exos inhibit apoptosis via microRNA-210,thereby improving the cardiac function of mice after MI and reducing MI area of mice,and playing a certain protective role in MI.