Regulation of macrophage cholesterol efflux and activation of liver X receptor by atorvastatin
- VernacularTitle:阿托伐他汀对巨噬细胞肝X受体表达及胆固醇外流的影响
- Author:
Zongjie QIAN
;
Lianfang ZHANG
;
Qiutang ZENG
;
Ling QIU
;
Chuanshi XIAO
- Publication Type:Journal Article
- Keywords:
Atorvastatin;
Cholesterol efflux;
Macrophages;
Receptors,liver X
- From:
Chinese Journal of Pathophysiology
2010;26(3):446-451
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To study the characteristic of liver X receptor alpha (LXRα), its target gene expression and cholesterol efflux in human macrophages treated with atorvastatin. METHODS: Human monocyte-derived macrophages were collected and cultured. Macrophages were treated with or without atorvastatin. Apolipoprotein A-I mediated human monocyte-derived macrophage cholesterol efflux was detected by liquid scintillation counting method. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of LXRα and some of its target genes ABCA1, SREBP2, CETP, PLTP, apoE, MMP-9 and MIP-1α. The protein expression of LXRα, ABCA1, MMP-9 and MIP-1α was determined by Western blotting. RESULTS: Pre-incubation of human monocyte-derived macrophages with atorvastatin dose dependently (1-2 μmol/L) stimulated cholesterol efflux mediated by apolipoprotein A-I. Atorvastatin also increased the mRNA expression of LXRα, ABCA1, SREBP2, CETP, PLTP, and protein expression of LXRα, ABCA1, but decreased the expression of MMP-9 and MIP-1α at both mRNA and protein levels. CONCLUSION: Atorvastatin enhances the cholesterol efflux, upregulates LXR and some genes associated with cholesterol metabolism and inhibits inflammatory responses in macrophages, indicating that statins may affect the formation of foam cells by activating LXR signaling pathway.
