Department of Internal Medicine, the Fourth Hospital of Zaozhuang City, Zaozhuang 277000, Shandong, PR China.
Department of Internal Medicine, Zaozhuang Municipal Hospital, Zaozhuang 277000, Shandong, PR China.
Microvasc Res. 2021 Nov;138:104215. doi: 10.1016/j.mvr.2021.104215. Epub 2021 Jun 24.
Cardiovascular disease, particularly coronary heart disease (CHD), is one of the diseases with the highest fatality. The close correlation between long non-coding RNAs (lncRNAs) and the occurrence and development of myocardial injury has been highlighted recently. This article mainly focused on the regulation of THRIL on myocardial injury caused by CHD in mice. After establishment of a mouse model with CHD, a lncRNA microarray analysis was performed on mouse myocardial tissues to detect differentially expressed lncRNAs, followed by RT-qPCR validation. CHD was induced in mice by high-fat diet feeding and THRIL was silenced using si-THRIL. The results showed that treating CHD mice with si-THRIL attenuated myocardial damage by restoring LVEF, LVFS, and HDL-C levels, while lowering HMI, LVMI, TC, TG, LDL-C, CK-MB, and cTnI levels. Meanwhile, mechanistical studies using bioinformatics prediction, dual-luciferase and subcellular fractionation assays revealed that THRIL bound to microRNA (miR)-424, inhibited miR-424 interaction with TXNIP and promoted TXNIP expression in the myocardial tissues. The cardioprotective effects of si-THRIL on mice were attenuated when miR-424 was downregulated. Moreover, TXNIP exerted its effects on myocardial injury by mediating the p53 pathway. Taken together, this study demonstrated that THRIL inhibition alleviates myocardial injury in CHD possibly through the miR-424/TXNIP/p53 axis.
心血管疾病,特别是冠心病(CHD),是死亡率最高的疾病之一。长链非编码 RNA(lncRNAs)与心肌损伤的发生和发展之间的密切关系最近受到了关注。本文主要关注 lncRNA THRIL 对 CHD 小鼠心肌损伤的调节作用。在建立 CHD 小鼠模型后,对小鼠心肌组织进行 lncRNA 微阵列分析,以检测差异表达的 lncRNAs,然后进行 RT-qPCR 验证。通过高脂饮食喂养诱导 CHD 小鼠,并使用 si-THRIL 沉默 THRIL。结果表明,用 si-THRIL 处理 CHD 小鼠可通过恢复 LVEF、LVFS 和 HDL-C 水平,降低 HMI、LVMI、TC、TG、LDL-C、CK-MB 和 cTnI 水平来减轻心肌损伤。同时,通过生物信息学预测、双荧光素酶报告基因和亚细胞分离测定等机制研究表明,THRIL 与 microRNA(miR)-424 结合,抑制 miR-424 与 TXNIP 的相互作用,并促进心肌组织中 TXNIP 的表达。当下调 miR-424 时,si-THRIL 对小鼠的心脏保护作用减弱。此外,TXNIP 通过介导 p53 通路发挥对心肌损伤的作用。综上所述,本研究表明,THRIL 抑制可能通过 miR-424/TXNIP/p53 轴减轻 CHD 中的心肌损伤。