Open AccessHyperhomocysteinemia-Induced Monocyte Chemoattractant Protein-1 Promoter DNA Methylation by Nuclear Factor-κB/DNA Methyltransferase 1 in Apolipoprotein E–Deficient Mice
Author(s) -
Wang Ju,
Yideng Jiang,
Yang Ai,
Weiwei Sun,
Chao Ma,
Shengchao Ma,
Huihui Gong,
Yujun Shi,
Jun Wei
Publication year - 2013
Publication title -
bioresearch open access
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 26
eISSN - 2164-7860
pISSN - 2164-7844
DOI - 10.1089/biores.2012.0300
Subject(s) - dnmt1 , dna methylation , dna methyltransferase , hyperhomocysteinemia , microbiology and biotechnology , methylation , methyltransferase , promoter , chemistry , monocyte , apolipoprotein b , biology , homocysteine , gene expression , dna , biochemistry , immunology , gene , cholesterol
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.