Department of Pathophysiology, Harbin Medical University-Daqing, No 39, Xin Yang Road, Daqing, Heilongjiang, 163319, China.
Department of Pharmacology, Harbin Medical University-Daqing, No 39, Xin Yang Road, Daqing, Heilongjiang, 163319, China.
Eur J Pharmacol. 2021 Oct 15;909:174403. doi: 10.1016/j.ejphar.2021.174403. Epub 2021 Jul 31.
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.
急性心肌梗死（AMI）是一种严重威胁人类健康的心血管疾病，但发病机制尚未完全阐明。本研究发现，微小 RNA-15a-5p（miR-15a-5p）在 AMI 中上调。miR-15a-5p 的敲低可降低缺氧处理的心肌细胞的细胞死亡率。此外，我们通过荧光素酶报告基因检测确定谷胱甘肽过氧化物酶 4（GPX4）是 miR-15a-5p 的直接靶标。miR-15a-5p 的过表达增强了铁死亡，从而加重了心肌细胞缺氧损伤。在机制上，沉默转录因子早期生长反应因子 1（Egr-1）抑制了 miR-15a-5p 的水平，增加了 GPX4 的蛋白表达，同时减少了铁死亡并减轻了心肌损伤。总之，这些结果为急性心肌梗死的进展提供了一个新的信号通路，即 Egr-1/miR-15a-5p/GPX4/铁死亡。
