Atherosclerosis (AS) is the main cause of coronary heart disease, in which enhancer of zeste homolog 2 (EZH2) has been implied to participate in this process. Thus, this work proposed to explore the effect of EZH2 on AS from microRNA‐139‐5p (miR‐139‐5p)/signal transducer and activator of transcription 1 (STAT1) axis. EZH2, miR‐139‐5p, and STAT1 expression in arterial tissues of AS patients were detected. Human arterial smooth muscle cells (HASMCs) induced with oxidized low‐density lipoprotein (ox‐LDL) and the mice fed with high fat diet were treated with silenced EZH2 or upregulated miR‐139‐5p to explore their roles in proliferation and apoptosis of HASMCs, together with inflammation response and oxidative stress of mice. Chromatin immunoprecipitation experiment was applied to verify the regulatory effect of EZH2 on miR‐139‐5p through methylation of H3K27me3. The targeting relationship between miR‐139‐5p and STAT1 was verified by online website and luciferase activity assay. Reduced miR‐139‐5p and overexpressed EHZ2 and STAT1 were found in AS. Silenced EZH2 or elevated miR‐139‐5p decreased the production of cholesterol and inhibited inflammation reaction in serum of mice with AS. Silenced EZH2 or elevated miR‐139‐5p facilitated proliferation and restrained apoptosis of ox‐LDL‐treated HASMCs, and restrained oxidative stress and cell apoptosis in arterial tissues of AS mice. EZH2 regulated miR‐139‐5p through H3K27me3, and miR‐139‐5p targeted STAT1. miR‐139‐5p silencing antagonized the effects of EZH2 down‐regulation on AS. This study manifests that down‐regulated EZH2 or elevated miR‐139‐5p inhibits ox‐LDL‐induced HASMCs apoptosis, plaque formation, and inflammatory response in AS mice, which may be related to down‐regulated STAT1.

中文翻译：

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zeste 同源物 2 的增强子通过调节 microRNA ‐139-5p 甲基化和信号转导和转录激活因子 1 的表达参与动脉粥样硬化过程

动脉粥样硬化 (AS) 是冠心病的主要原因，其中 zeste 同源物 2 (EZH2) 的增强子被暗示参与了这一过程。因此，这项工作提出从 microRNA-139-5p (miR-139-5p)/信号转导和转录激活因子 1 (STAT1) 轴探索 EZH2 对 AS 的影响。检测 AS 患者动脉组织中 EZH2、miR-139-5p 和 STAT1 的表达。用沉默的 EZH2 或上调的 miR-139-5p 处理氧化低密度脂蛋白 (ox-LDL) 诱导的人动脉平滑肌细胞 (HASMCs) 和喂食高脂肪饮食的小鼠，以探索它们在 HASMCs 增殖和凋亡中的作用，以及小鼠的炎症反应和氧化应激。染色质免疫沉淀实验通过H3K27me3甲基化验证EZH2对miR-139-5p的调控作用。miR-139-5p与STAT1的靶向关系通过在线网站和荧光素酶活性测定进行验证。在 AS 中发现了减少的 miR-139-5p 和过表达的 EHZ2 和 STAT1。沉默的 EZH2 或升高的 miR-139-5p 降低了 AS 小鼠血清中胆固醇的产生并抑制了炎症反应。沉默的 EZH2 或升高的 miR-139-5p 促进了 ox-LDL 处理的 HASMCs 的增殖和抑制凋亡，并抑制了 AS 小鼠动脉组织中的氧化应激和细胞凋亡。EZH2 通过 H3K27me3 调节 miR-139-5p，而 miR-139-5p 靶向 STAT1。miR-139-5p 沉默拮抗 EZH2 下调对 AS 的影响。