miR‐26a attenuates cardiac apoptosis and fibrosis by targeting ataxia–telangiectasia mutated in myocardial infarction

Apoptosis 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. Our study demonstrated that ataxia–telangiectasia mutated (ATM) is the target for miR‐26a. miR‐26a attenuated cardiac apoptosis and fibrosis by targeting ATM both in vitro and in vivo. Additionally, miR‐26a regulated the expression of collagen type I and connective tissue growth factor (CTGF). We elucidated the role and function of miR‐26a in cardiac apoptosis and fibrosis, suggesting that miR‐26a may lead to a new therapeutic intervention in heart disease.