The Egr-1/miR-15a-5p/GPX4 axis regulates ferroptosis in acute myocardial infarction

Acute myocardial infarction (AMI) is a type of cardiovascular diseases that severely threatens human being, but the mechanisms have not been thoroughly clarified. Here, we detected that microRNA-15a-5p (miR-15a-5p) was up-regulated in AMI. Knockdown of miR-15a-5p reduced cell mortality in hypoxic-treated myocardial cells. In addition, we determined that glutathione peroxidase4 (GPX4) was the direct target of miR-15a-5p by luciferase reporter assay. Over-expression of miR-15a-5p strengthened ferroptosis, then aggravated myocardial cell hypoxia injury. Mechanistically, silencing transcription factor early growth response-1 (Egr-1) inhibited the level of miR-15a-5p, increased the protein expression of GPX4, accompanied by reduced ferroptosis and alleviated myocardial injury. In summary, these results provide a novel signaling pathway during the progression of acute myocardial infarction, namely Egr-1/miR-15a-5p/GPX4/ferroptosis.