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.