High-methionine diets accelerate atherosclerosis by HHcy-mediated FABP4 gene demethylation pathway via DNMT1 in ApoE-/- mice
High-methionine diets accelerate atherosclerosis by HHcy-mediated FABP4 gene demethylation pathway via DNMT1 in ApoE-/- mice
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高蛋氨酸饮食通过 DNMT1 介导的 HHcy 介导的 FABP4 基因去甲基化途径加速 ApoE(-/-) 小鼠的动脉粥样硬化
DOI：
10.1016/j.febslet.2015.11.010
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发表时间：
2015-12-21
期刊：
影响因子：
3.5
通讯作者：
Jiang, Yi-Deng
中科院分区：
文献类型：
--
作者：
Yang, An-Ning;Zhang, Hui-Ping;Jiang, Yi-Deng
同型半胱氨酸(Hcy)是动脉粥样硬化的独立危险因素，但其潜在的分子机制尚不清楚。我们研究了Hcy对脂肪酸结合蛋白4(FABP4)的影响，并验证了我们的假设，即Hcy诱导的动脉粥样硬化是通过增加FABP4的表达和减少甲基化来介导的。观察高蛋氨酸饮食喂养20周后，ApoE(-/-)小鼠主动脉中FABP4的表达和DNA甲基化情况。FABP4的过表达促进了总胆固醇和胆固醇酯在泡沫细胞中的积累。DNA甲基转移酶1(DNMT1)的上调促进了甲基化过程，降低了FABP4的表达。这些数据表明，FABP4在Hcy介导的脂代谢紊乱中起关键作用，DNMT1可能是Hcy相关动脉粥样硬化的一个新的治疗靶点。(C)2015年欧洲生化学会联合会。爱思唯尔出版，版权所有。
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.