Folate and ApoE DNA methylation induced by homocysteine in human monocytes.
Homocysteine (Hcy) is an important and independent risk factor for arteriosclerosis, and apolipoprotein E (ApoE) is an important gene of anti atherosclerosis, but the characteristics and their key links that are involved in their pathogenic mechanisms are still poorly understood. The objective of the present study was to investigate the effects of Hcy and folate on ApoE as well as the underlying mechanism of ApoE expression induced by Hcy in monocytes. When clinically relevant concentrations of Hcy and folate were added to the cultured monocytes for 4 days, we found that clinically relevant Hcy (100 microM) may increase the levels of total cholesterol (TC), free cholesterol (FC), and cholesteryl ester (CE), and also decrease ApoE mRNA, protein expressions, leading to 34.28%, 45.00% in cultured primary human monocytes in comparison to the positive group. The effects of Hcy were primarily mediated by C-5 MTase, because Hcy could upregulate the activity of C-5 MTase and then accelerate DNA methylation of ApoE. However, folate decreased the levels of TC, FC, and CE (p < 0.001) and increased the ApoE expression; as to say, folate primarily repressed the effects of DNA methylation induced by Hcy and reduced anti atherosclerosis. In conclusion, these results suggested that ApoE DNA methylation that is induced by Hcy may play a potential role for ApoE expression in atherosclerosis. Folate has beneficial effects for anti atherosclerosis, and it may become a therapeutic target for preventing Hcy-induced atherosclerosis.
Yi-Deng
Jiang
J
Department of Pathophysiology, Ning Xia Medical College, Yin Chuan, China. jwcjyd@163.com
Tao
Sun
S
Hui-Ping
Zhang
Z
Jian-Tuan
Xiong
X
Jun
Cao
C
Gui-Zhong
Li
L
Shu-Ren
Wang
W
D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D005487:Foam Cells / Q000166:cytology; D005492:Folic Acid / Q000235:genetics / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D050356:Lipid Metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic
D001057:Apolipoproteins E; D006710:Homocysteine; D005492:Folic Acid; D002784:Cholesterol; D004248:DNA (Cytosine-5-)-Methyltransferases