Ibrolipim increases ABCA1/G1 expression by the LXRα signaling pathway in THP-1 macrophage-derived foam cells

被引:31
作者
Chen, Si-guo [1 ,3 ]
Xiao, Ji [1 ,2 ]
Liu, Xie-hong [1 ]
Liu, Mei-mei [1 ]
Mo, Zhong-cheng [1 ]
Yin, Kai [1 ]
Zhao, Guo-jun [1 ]
Jiang, Jin [1 ]
Cui, Li-bao [1 ]
Tan, Chun-zhi [1 ]
Yin, Wei-dong [1 ]
Tang, Chao-ke [1 ]
机构
[1] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China
[2] Univ S China, Dept Anesthesiol, Affiliated Hosp 2, Hengyang 421001, Peoples R China
[3] Xiangnan Univ, Dept Physiol, Chenzhou 423000, Peoples R China
关键词
ATP-binding membrane cassette transporter A-1; ATP-binding membrane cassette transporter G-1; ibrolipim; liver X receptor alpha; atherosclerosis; RNA interference; high density lipoprotein; apolipoprotein; cholesterol; REVERSE CHOLESTEROL TRANSPORT; TANGIER-DISEASE; BINDING; EFFLUX; ABCG1; GENE; NO-1886; MORTALITY; A1; C1;
D O I
10.1038/aps.2010.166
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Aim: To determine the effects and potential mechanisms of ibrolipim on ATP-binding membrane cassette transporter A-1 (ABCA1) and ATP-binding membrane cassette transporter G-1 (ABCG1) expression from human macrophage foam cells, which may play a critical role in atherogenesis. Methods: Human THP-1 cells pre-incubated with ox-LDL served as foam cell models. Specific mRNA was quantified using real-time RTPCR and protein expression using Western blotting. Cellular cholesterol handling was studied using cholesterol efflux experiments and high performance liquid chromatography assays. Results: Ibrolipim 5 and 50 mu mol/L significantly increased cholesterol efflux from THP-1 macrophage-derived foam cells to apoA-I or HDL. Moreover, it upregulated the expression of ABCA1 and ABCG1. In addition, LXR alpha was also upregulated by the ibrolipim treatment. In addition, LXRa small interfering RNA completely abolished the promotion effect that was induced by ibrolipim. Conclusion: Ibrolipim increased ABCA1 and ABCG1 expression and promoted cholesterol efflux, which was mediated by the LXRa signaling pathway.
引用
收藏
页码:1343 / 1349
页数:7
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