Homocysteine-mediated cholesterol efflux via ABCA1 and ACAT1 DNA methylation in THP-1 monocyte-derived foam cells

Yu Liang, Xiaoling Yang, Linna Ma, Xin Cai, Lei Wang, Cheng Yang, Guizhong Li, Minghao Zhang, Weiwei Sun and Yideng Jiang

Acta Biochim Biophys Sin 2013,Mar; 45(3): 220–228; doi: 10.1093/abbs/gms119

Department of Laboratory Medicine, Ningxia Medical University, Yinchuan 750004, China

Homocysteine (Hcy) has been recognized as a prevalent risk factor for cardiovascular events. Cholesterol-loaded foam cells are a central component of atherosclerotic lesions. ATP-binding cassette transporter A1 (ABCA1), which mediates the efflux of cellular cholesterol and phospholipids, is the rate-limiting step in lipid metabolism. Acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) promotes accumulation of cholesterol ester in macrophages, thereby resulting in the foam cell formation, a hallmark of early stage in atherosclerosis. In this study, cultured monocyte-derived foam cells were incubated with clinical relevant concentrations of Hcy for 24 h. Both increased number of foam cells and accumulation of cholesterol were found, and the mRNA and protein expression levels of ABCA1 were decreased, while ACAT1 expression was increased in the presence of Hcy. Furthermore, the DNA methylation level of ABCA1 gene was increased whereas ACAT1 DNA methylation was decreased by using different concentrations of Hcy. Moreover, our results showed that DNA methyltransferase (DNMT) activity and DNA methyltransferase 1 (DNMT1) mRNA expression were increased by Hcy. It is indicated that DNA methylation has the function to regulate the expression of ABCA1 and ACAT1 via DNMT. In conclusion, these results suggest that ABCA1 and ACAT1 DNA methylation induced by Hcy may play a potential role in ABCA1 and ACAT1 expression and the accumulation of cholesterol in monocyte-derived foam cells.

图例: 高半胱氨酸对ABCA1和ACAT1表达的影响

全文: http://abbs.oxfordjournals.org/content/45/3/220.full 

与此文相关的文献:

1 Endoplasmic reticulum oxidoreductin 1α mediates hepatic endoplasmic reticulum stress in homocysteine-induced atherosclerosis

2 Hyperhomocysteinemia induces cardiac injury by up-regulation of p53-dependent Noxa and Bax expression through the p53 DNA methylation in ApoE−/− mice