Department of Cardiology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huang Shi, 435000, China.
Center for Animal Experiment, Wuhan University, Wuhan, 430000, China.
Eur J Pharmacol. 2020 Jul 5;878:173092. doi: 10.1016/j.ejphar.2020.173092. Epub 2020 Mar 29.
During the processes of myocardial ischemia reperfusion (I/R) injury, inflammation and apoptosis play an important role. I/R and its induced acute myocardial infarction (AMI) with high morbidity and mortality, and there is no effective treatment for it so far. TRAF5 has been shown to regulate inflammation and apoptosis in atherosclerosis, steatosis and melanoma cells, but its function in myocardial I/R injury is still unclear. This study demonstrates that the expression of TRAF5 is significant up-regulation in heart tissues of I/R injury mice and hypoxia/reoxygenation (H/R)-stimulated cardiomyocytes. TRAF5 knockout mice exhibites heavier heart damage, inflammatory response and cell death after myocardial I/R injury. Further, TRAF5 overexpression inhibites inflammation and apoptosis of H/R-stimulated cardiomyocytes. Mechanistically, we prove that TRAF5 promotes the activation of AKT. Overall, our study indicates that TRAF5 can regulate the processes of myocardial I/R injury. TRAF5 can be a new therapy target for myocardial I/R injury.
在心肌缺血再灌注(I/R)损伤过程中,炎症和细胞凋亡起着重要作用。I/R 及其诱导的急性心肌梗死(AMI)具有高发病率和死亡率,目前尚无有效的治疗方法。TRAF5 已被证明可调节动脉粥样硬化、脂肪变性和黑色素瘤细胞中的炎症和细胞凋亡,但它在心肌 I/R 损伤中的作用尚不清楚。本研究表明,TRAF5 的表达在 I/R 损伤小鼠和缺氧/复氧(H/R)刺激的心肌细胞中的心脏组织中显著上调。TRAF5 基因敲除小鼠在心肌 I/R 损伤后表现出更严重的心脏损伤、炎症反应和细胞死亡。此外,TRAF5 的过表达抑制了 H/R 刺激的心肌细胞中的炎症和细胞凋亡。从机制上讲,我们证明 TRAF5 促进了 AKT 的激活。总的来说,我们的研究表明 TRAF5 可以调节心肌 I/R 损伤过程。TRAF5 可以成为心肌 I/R 损伤的新治疗靶点。