Department of Cardiology, the Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.
Department of Cardiology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.
J Cardiovasc Pharmacol. 2020 Sep;76(3):305-312. doi: 10.1097/FJC.0000000000000867.
Myocardial cell death during acute myocardial infarction occurs because of acute ischemia, persistent ischemia, reperfusion-associated injury, and the inflammatory infiltrate as a response to cell necrosis. In the present study, quantitative real-time PCR showed that lncRNA Gm4419 was highly upregulated in ischemia/reperfusion myocardial tissues and hypoxia/reoxygenation H9C2 cells, whereas miR-682 was downregulated. Knocking down Gm4419 with sh-Gm4419 resulted in the rescue of myocardial infarction and apoptosis induced by ischemia/reperfusion or hypoxia/reoxygenation. Our study further demonstrated that Gm4419 may bind with miR-682 directly. Moreover, in vitro experiments further demonstrated that miR-682 could bind to tumor necrosis factor receptor-associated factor 3 (TRAF3) directly. Most importantly, TRAF3 overexpression could counteract the effect of sh-Gm4419. Taken together, our study indicated that Gm4419 may target miR-682 via sponging to increase TRAF3 expression, thereby contributing to myocardial I/R injury. Therefore, the Gm4419/miR-682/TRAF3 axis may be an important regulatory mechanism in myocardial ischemia/reperfusion injury.
在急性心肌梗死中，心肌细胞死亡是由于急性缺血、持续缺血、再灌注相关损伤以及作为细胞坏死反应的炎症浸润引起的。在本研究中，实时定量 PCR 显示，lncRNA Gm4419 在缺血/再灌注心肌组织和缺氧/复氧 H9C2 细胞中高度上调，而 miR-682 下调。用 sh-Gm4419 敲低 Gm4419 可挽救缺血/再灌注或缺氧/复氧诱导的心肌梗死和细胞凋亡。我们的研究进一步表明，Gm4419 可能直接与 miR-682 结合。此外，体外实验进一步表明，miR-682 可以直接与肿瘤坏死因子受体相关因子 3 (TRAF3) 结合。最重要的是，TRAF3 的过表达可以抵消 sh-Gm4419 的作用。总之，我们的研究表明，Gm4419 可能通过海绵作用靶向 miR-682 来增加 TRAF3 的表达，从而导致心肌 I/R 损伤。因此，Gm4419/miR-682/TRAF3 轴可能是心肌缺血/再灌注损伤的重要调节机制。
