High-methionine diets accelerate atherosclerosis by HHcy-mediated FABP4 gene demethylation pathway via DNMT1 in ApoE(-/-) mice
An-Ning Yang, Hui-Ping Zhang, Yue Sun, Xiao-Ling Yang, Nan Wang, Guangrong Zhu, Hui Zhang, Hua Xu, Sheng-Chao Ma, Yue Zhang, Gui-Zhong Li, Yue-Xia Jia, Jun Cao, Yi-Deng Jiang, An-Ning Yang, Hui-Ping Zhang, Yue Sun, Xiao-Ling Yang, Nan Wang, Guangrong Zhu, Hui Zhang, Hua Xu, Sheng-Chao Ma, Yue Zhang, Gui-Zhong Li, Yue-Xia Jia, Jun Cao, Yi-Deng Jiang
Abstract
Homocysteine (Hcy) is an independent risk factor for atherosclerosis, but the underlying molecular mechanisms are not known. We investigated the effects of Hcy on fatty acid-binding protein 4 (FABP4), and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased FABP4 expression and decreased methylation. The FABP4 expression and DNA methylation was assessed in the aorta of ApoE(-/-) mice fed high-methionine diet for 20weeks. Over-expression of FABP4 enhanced accumulation of total cholesterol and cholesterol ester in foam cells. The up-regulation of DNA methyltransferase 1 (DNMT1) promoted the methylation process and decreased FABP4 expression. These data suggest that FABP4 plays a key role in Hcy-mediated disturbance of lipid metabolism and that DNMT1 may be a novel therapeutic target in Hcy-related atherosclerosis.
Keywords: Atherosclerosis; DNA methylation; Fatty acid-binding protein 4; Foam cell; Homocysteine.
Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Source: PubMed