MiR‐34a Targets HDAC1‐Regulated H3K9 Acetylation on Lipid Accumulation Induced by Homocysteine in Foam Cells. Issue 12 (12th June 2017)

• Record Type: Journal Article
• Authors: Zhao, Qingguo; Li, Shuqiang; Li, Nan; Yang, Xiaoling; Ma, Shengchao; Yang, Anning; Zhang, Hui; Yang, Songhao; Mao, Caiyan; Xu, Lingbo; Gao, Tingting; Yang, Xiaoming; Zhang, Huiping; Jiang, Yideng
• Is Part Of: Journal of cellular biochemistry. Volume 118:Issue 12(2017)
• Page Start: 4617
• Page End: 4627
• Publication Date: 2017-06-12
• Subjects: HYPERHOMOCYSTEINEMIA -- microRNA -- HISTONE ACETYLATION -- HISTONE DEACETYLASE 1 -- LIPID ACCUMULATION; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26126
• Languages: English
• ISSNs: 0730-2312

Abstract

ABSTRACT: Hyperhomocysteinemia (HHcy) promotes atherogenesis by modification of histone acetylation patterns and regulation of miRNA expression while the underlying molecular mechanisms are not well known. In this study, we investigated the effects of homocysteine (Hcy) on the expression of histone deacetylase 1 (HDAC1) and tested our hypothesis that Hcy‐induced atherosclerosis is mediated by increased HDAC1 expression, which is regulated by miR‐34a. The expression of HDAC1 increased and acetylation of histone H3 at lysine 9 (H3K9ac) decreased in the aorta of ApoE −/− mice fed with high methionine diet, whereas miR‐34a expression was inhibited. Over‐expression of HDAC1 inhibited H3K9ac level and promoted the accumulation of total cholesterol, free cholesterol, and triglycerides in the foam cells. Furthermore, up‐regulation of miR‐34a reduced HDAC1 expression and inhibited the accumulation of total cholesterol (TC), free cholesterol (FC), and triglycerides (TG) in the foam cells. These data suggest that HDAC1‐related H3K9ac plays a key role in Hcy‐mediated lipid metabolism disorders, and that miR‐34a may be a novel therapeutic target in Hcy‐related atherosclerosis. J. Cell. Biochem. 118: 4617–4627, 2017. © 2017 Wiley Periodicals, Inc. Abstract : Our research demonstrates that elevating Hcy triggers the level descending of miR‐34a which detain H3K9 acetylation through HDAC1, eventually impulse aberrant lipid accumulation during the development of As.