SNF5 promotes IL-1β expression via H3K4me1 in atherosclerosis induced by homocysteine. (June 2021)

• Record Type: Journal Article
• Authors: Xie, Lin; Ding, Ning; Zhang, Honghong; Liu, Kun; Xiong, Jiantuan; Ma, Shengchao; Yang, Anning; Zhang, Huiping; Jiang, Yideng
• Is Part Of: International journal of biochemistry & cell biology. Volume 135(2021)
• Publication Date: 2021-06
• Subjects: Atherosclerosis -- Homocysteine -- SNF5 -- IL-1β -- H3K4me1; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2021.105974
• Languages: English
• ISSNs: 1357-2725

Abstract

Highlights: SNF5 promotes macrophage inflammation via IL-1β during the atherosclerotic plaque formation. SNF5 bind to KDM1A to promote H3K4me1 on IL-1β, which led to enhanced production of IL-1β in the process of atherosclerotic plaque formation. Hcy accelerates atherosclerosis by promoting the production of IL-1β, IL-6 and TNF-α. Abstract: 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.