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姜黄素通过抑制 lncRNA MIAT 对 miR-124 的表观遗传抑制作用改善动脉粥样硬化。

Curcumin improves atherosclerosis by inhibiting the epigenetic repression of lncRNA MIAT to miR-124.

机构信息

Department of Interventional Vascular Surgery, People's Hospital of Hunan Province, Changsha, China.

Department of Spinal Rehabilitation, Xiangya Boai Rehabilitation Hospital, Changsha, China.

出版信息

Vascular. 2022 Dec;30(6):1213-1223. doi: 10.1177/17085381211040974. Epub 2022 Jan 6.

DOI:10.1177/17085381211040974
PMID:34989253
Abstract

Atherosclerosis is a dominant cardiovascular disease. Curcumin has protective effect on atherosclerosis. However, the mechanisms remain to be explored. Atherosclerosis was induced by feeding mice with high-fat diet (HFD) and ox-low-density lipoprotein (LDL)-induced human umbilical vein endothelial cells (HUVECs) were structured. Oil Red O staining was used to evaluate the plaques in the artery. Quantitative real-time PCR (qRT-PCR) was conducted to detect the level of myocardial infarction associated transcript (MIAT), miR-124, and enhancer of zeste homolog 2 (EZH2). We performed western blotting and enzyme linked immunosorbent assay to examine the expression of EZH2 and cytokines including IL-1β, TNFα, IL-6, and IL-8, respectively. RNA immunoprecipitation and chromatin immunoprecipitation (ChIP) were used to validate the interaction between myocardial infarction associated transcript and EZH2. Flow cytometry and CCK-8 assay were used to examine cell apoptosis and proliferation, respectively. Curcumin suppressed inflammation in atherosclerosis mouse model and ox-LDL-induced cell model. MIAT overexpression and miR-124 inhibition relieved the anti-inflammation effect of curcumin in ox-LDL-induced cell. MIAT regulated miR-124 by interacting with EZH2. Curcumin relieved ox-LDL-induced cell inflammation via regulating MIAT/miR-124 pathway. MIAT/miR-124 axis mediated the effect of curcumin on atherosclerosis and altered cell apoptosis and proliferation, both and . These data further support the application of curcumin in control of atherosclerosis advancement.

摘要

动脉粥样硬化是一种主要的心血管疾病。姜黄素对动脉粥样硬化有保护作用。然而,其机制仍有待探索。通过给小鼠喂食高脂肪饮食(HFD)诱导动脉粥样硬化,构建人脐静脉内皮细胞(HUVEC)氧化低密度脂蛋白(ox-LDL)模型。油红 O 染色用于评估动脉中的斑块。实时定量 PCR(qRT-PCR)用于检测心肌梗塞相关转录物(MIAT)、miR-124 和增强子的水平。我们进行了 Western blot 和酶联免疫吸附试验,以检测 EZH2 和细胞因子(包括 IL-1β、TNFα、IL-6 和 IL-8)的表达。采用 RNA 免疫沉淀和染色质免疫沉淀(ChIP)验证 MIAT 与 EZH2 的相互作用。流式细胞术和 CCK-8 检测分别用于检测细胞凋亡和增殖。姜黄素抑制动脉粥样硬化小鼠模型和 ox-LDL 诱导的细胞模型中的炎症。MIAT 过表达和 miR-124 抑制减轻了 ox-LDL 诱导的细胞中姜黄素的抗炎作用。MIAT 通过与 EZH2 相互作用调节 miR-124。姜黄素通过调节 MIAT/miR-124 通路缓解 ox-LDL 诱导的细胞炎症。MIAT/miR-124 轴介导了姜黄素对动脉粥样硬化的作用,并改变了细胞凋亡和增殖。这些数据进一步支持了姜黄素在控制动脉粥样硬化进展中的应用。

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