Chiang, Ming-HsienMing-HsienChiangLiang, Chan-JungChan-JungLiangLin, Lung-ChunLung-ChunLinYang, Yi-FanYi-FanYangCHING-CHANG HUANGYING-HSIEN CHENHSIEN-LI KAOChen, Yu-ChenYu-ChenChenKe, Shin-RongShin-RongKeLee, Chiang-WenChiang-WenLeeMAO-SHIN LINYUH-LIEN CHEN2020-12-302020-12-302020-090021-95411097-4652https://scholars.lib.ntu.edu.tw/handle/123456789/535723Apoptosis and fibrosis play a vital role in myocardial infarction (MI) induced tissue injury. Although microRNAs have been the focus of many studies on cardiac apoptosis and fibrosis in MI, the detailed effects of miR-26a is needed to further understood. The present study demonstrated that miR-26a was downregulated in ST-elevation MI (STEMI) patients and oxygen-glucose deprivation (OGD)-treated H9c2 cells. Downregulation of miR-26a was closely correlated with the increased expression of creatine kinase, creatine kinase-MB and troponin I in STEMI patients. Further analysis identified that ataxia-telangiectasia mutated (ATM) was a target gene for miR-26a based on a bioinformatics analysis. miR-26a overexpression effectively reduced ATM expression, apoptosis, and apoptosis-related proteins in OGD-treated H9c2 cells. In a mouse model of MI, the expression of miR-26a was significantly decreased in the infarct zone of the heart, whereas apoptosis and ATM expression were increased. miR-26a overexpression effectively reduced ATM expression and cardiac apoptosis at Day 1 after MI. Furthermore, we demonstrated that overexpression of miR-26a improved cardiac function and reduced cardiac fibrosis by the reduced expression of collagen type I and connective tissue growth factor (CTGF) in mice at Day 14 after MI. Overexpression of miR-26a or ATM knockdown decreased collagen I and CTGF expression in cultured OGD-treated cardiomyocytes. Taken together, these data demonstrate a prominent role for miR-26a in linking ATM expression to ischemia-induced apoptosis and fibrosis, key features of MI progression. miR-26a reduced MI development by affecting ATM expression and could be targeted in the treatment of MI.enapoptosis; ataxia-telangiectasia mutated; fibrosis; miR-26a; myocardial infarctionapoptosis; ataxia–telangiectasia mutated; fibrosis; miR-26a; myocardial infarction[SDGs]SDG3ATM protein; caspase 3; collagen type 1; connective tissue growth factor; creatine kinase; creatine kinase MB; microRNA; microRNA 26a; protein p53; troponin I; ATM protein; CCN2 protein, mouse; connective tissue growth factor; glucose; microRNA; MIRN26 microRNA, rat; oxygen; animal cell; animal experiment; animal model; apoptosis; Article; bioinformatics; clinical article; controlled study; down regulation; gene expression level; H9c2(2-1) cell line; heart function; heart muscle fibrosis; human; male; mouse; nonhuman; priority journal; protein blood level; protein function; protein phosphorylation; ST segment elevation myocardial infarction; animal; apoptosis; cardiac muscle; cardiac muscle cell; disease model; fibrosis; genetics; heart infarction; metabolism; pathology; rat; Animals; Apoptosis; Ataxia Telangiectasia Mutated Proteins; Connective Tissue Growth Factor; Disease Models, Animal; Fibrosis; Glucose; Humans; Mice; MicroRNAs; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Oxygen; Rats10.1002/jcp.2953731990056