High-methionine diets accelerate atherosclerosis by HHcy-mediated FABP4 gene demethylation pathway via DNMT1 in ApoE-/- mice

被引：55

作者：

Yang, An-Ning ^{[1
]}

Zhang, Hui-Ping ^{[4
]}

Sun, Yue ^{[1
,4
]}

Yang, Xiao-Ling ^{[1
,4
]}

Wang, Nan ^{[1
]}

Zhu, Guangrong ^{[1
]}

Zhang, Hui ^{[2
]}

Xu, Hua ^{[1
,4
]}

Ma, Sheng-Chao ^{[2
]}

Zhang, Yue ^{[3
,4
]}

Li, Gui-Zhong ^{[1
,4
]}

Jia, Yue-Xia ^{[1
]}

Cao, Jun ^{[1
]}

Jiang, Yi-Deng ^{[1
,4
]}

机构：

[1] Ningxia Med Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Yinchuan, Peoples R China

[2] Ningxia Med Univ, Dept Inspect Coll, Yinchuan, Peoples R China

[3] Ningxia Med Univ, Dept Foreign Language Teaching, Yinchuan, Peoples R China

[4] Ningxia Med Univ, Prenatal Diag Ctr, Gen Hosp, Yinchuan, Peoples R China

来源：

FEBS LETTERS | 2015年 / 589卷 / 24期

基金：

中国国家自然科学基金;

关键词：

Homocysteine; Atherosclerosis; Foam cell; Fatty acid-binding protein 4; DNA methylation; BINDING PROTEIN 4; DNA METHYLATION; PPAR-GAMMA; HYPERHOMOCYSTEINEMIA; EXPRESSION; DIFFERENTIATION; HOMOCYSTEINE; MACROPHAGES; DISEASE; ADIPOGENESIS;

D O I：

10.1016/j.febslet.2015.11.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 20 weeks. Over-expression of FABP4 enhanced accumulation of total cholesterol and cholesterol ester in foam cells. The upregulation 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. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：3998 / 4009

页数：12

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