title: Hyperhomocysteinemia-Induced Monocyte Chemoattractant Protein-1 Promoter DNA Methylation by Nuclear Factor-κB/DNA Methyltransferase 1 in Apolipoprotein E-Deficient Mice.
abstract: Hyperhomocysteinemia is considered to be a significant risk factor in atherosclerosis and plays an important role in it. The purpose of this study was to determine the molecular mechanism of blood monocyte chemoattractant protein-1 (MCP-1) promoter DNA hypomethylation in the formation of atherosclerosis induced by hyperhomocysteinemia, and to explore the effect of nuclear factor-κB (NF-κB)/DNA methyltransferase 1 (DNMT1) in this mechanism. The atherosclerotic effect of MCP-1 in apolipoprotein E-deficient (ApoE(-/-)) and wild-type C57BL/6J mice was evaluated using atherosclerotic lesion area; serum NF-κB, MCP-1, and DNMT1 levels; and MCP-1 promoter DNA methylation expression. In vitro, the mechanism responsible for the effect of NF-κB/DNMT1 on foam cells was investigated by measuring NF-κB and DNMT1 levels to determine whether NF-κB/DNMT1 had an effect on gene expression. Compared with the control group, atherosclerotic lesions in ApoE(-/-) mice fed a high methionine diet significantly increased, as did the expression of MCP-1. In vitro study showed that pyrrolidine dithiocarbamate treatment down-regulated levels of NF-κB and raised DNMT1 concentrations, confirming the effect of NF-κB/DNMT1 in the MCP-1 promoter DNA methylation process. In conclusion, our results suggest that through NF-κB/DNMT1, MCP-1 promoter DNA hypomethylation may play a key role in formation of atherosclerosis under hyperhomocysteinemia.
authors.affiliation: Department of Inspection, Ningxia Medical University , Yinchuan, China .
authors.forename: Ju
authors.initials: J
authors.lastname: Wang
authors.forename: Yideng
authors.initials: Y
authors.lastname: Jiang
authors.forename: Anning
authors.initials: A
authors.lastname: Yang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Sun
authors.forename: Changjian
authors.initials: C
authors.lastname: Ma
authors.forename: Shengchao
authors.initials: S
authors.lastname: Ma
authors.forename: Huihui
authors.initials: H
authors.lastname: Gong
authors.forename: Yingkang
authors.initials: Y
authors.lastname: Shi
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
keywords: DNA methylation; atherosclerosis; hyperhomocysteinemia; monocyte chemoattractant protein-1