Asymmetric dimethylarginine upregulates the expression of ACAT-1 in THP-1 macrophage-derived foam cells.
- Author:
Zhen-dong ZHU
1
;
Jun-qin JIA
;
Xuan ZHANG
;
Yong-jin WANG
;
Dian-hua WANG
Author Information
- Publication Type:Journal Article
- MeSH: Acetyl-CoA C-Acetyltransferase; metabolism; Arginine; analogs & derivatives; pharmacology; Cell Line; Cholesterol; analysis; Foam Cells; cytology; metabolism; Humans; Macrophages; cytology; drug effects; metabolism; Monocytes; cytology; drug effects; RNA, Messenger; genetics; Up-Regulation
- From: Journal of Southern Medical University 2010;30(12):2613-2618
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo investigate the effects of asymmetric dimethylarginine (ADMA) on ACAT-1 expression and cholesterol content in THP-1-derived macrophages and foam cells.
METHODSTHP-1 cells were induced to differentiate into macrophages and further into foam cells. The macrophages and foam cells were exposed to different concentrations (0, 3.75, 7.5, 15, and 30 µmol/L) of ADMA for varying time lengths (6, 12, and 24 h), and the changes in ACAT-1 mRNA and protein levels in the cells were measured with RT-PCR and Western blotting. The cellular cholesterol content was measured with enzyme-linked colorimetry assay.
RESULTSIn THP-1-derived macrophages and foam cells, the expression levels of ACAT-1 mRNA and protein and cellular cholesterol content increased significantly in response to ADMA treatment in a time- and concentration-dependent manner.
CONCLUSIONADMA may play an important role in inducing foam cell formation from macrophages. ACAT-1 inhibition targeting the macrophages and foam cells may serve as a potential therapeutic target in the treatment of atherosclerosis.
