Homocysteine (Hcy) is a strong and independent risk factor of atherosclerosis. It can accelerate atherosclerosis through increased production of inflammatory factors, especially interleukin-1 β (IL-1β), while the precise mechanisms remain to be well elucidated. In this study, we investigated the role of the tumor suppressor gene SNF5 related to switch/sucrose non-fermentable complex (SWI/SNF) in the occurrence and development of atherosclerosis induced by Hcy. Using Hyperhomocysteinemia (HHcy) atherosclerotic model with apolipoprotein E knockout (ApoE^−/−) mice fed with high-methionine diet, we showed that Hcy aggravates inflammation in macrophages during the atherosclerotic plaque formation. Further analysis showed that SNF5 promotes IL-1β expression and secretion. In addition, due to the existence of H3K4 methylation signals in the vicinity of IL-1β, we found that Hcy significantly promotes the expression of H3K4me1, and lysine-specific histone demethylase 1A (KDM1A) acts as a transcriptional repressor to regulate the expression of H3K4me1 by demethylating H3K4me1. In summary, our results demonstrated that Hcy up-regulates the expression of SNF5 through KDM1A, resulting in an increased level of H3K4me1 modification and IL-1β in macrophages, which in turn promotes the formation of atherosclerosis. Our study will provide more evidence for further revealing the specific mechanism of Hcy-induced inflammation and the diagnosis, prevention, and treatment of atherosclerosis.

同型半胱氨酸 (Hcy) 是动脉粥样硬化的强且独立的危险因素。它可以通过增加炎症因子，尤其是白细胞介素 1 β (IL-1β) 的产生来加速动脉粥样硬化，但其确切机制仍有待阐明。在本研究中，我们研究了与开关/蔗糖不可发酵复合物（SWI/SNF）相关的抑癌基因 SNF5 在 Hcy 诱导的动脉粥样硬化发生和发展中的作用。使用高同型半胱氨酸血症 (HHcy) 动脉粥样硬化模型与载脂蛋白 E 敲除 (ApoE ^-/-) 用高蛋氨酸饮食喂养的小鼠，我们发现 Hcy 在动脉粥样硬化斑块形成过程中加剧了巨噬细胞的炎症。进一步分析表明，SNF5 促进 IL-1β 的表达和分泌。此外，由于IL-1β附近存在H3K4甲基化信号，我们发现Hcy显着促进H3K4me1的表达，赖氨酸特异性组蛋白去甲基化酶1A（KDM1A）作为转录抑制因子调节H3K4me1的表达。 H3K4me1 通过去甲基化 H3K4me1。总之，我们的结果表明，Hcy 通过 KDM1A 上调 SNF5 的表达，导致巨噬细胞中 H3K4me1 修饰和 IL-1β 水平增加，进而促进动脉粥样硬化的形成。