Lipoxin A4 promotes ABCA1 expression and cholesterol efflux through the LXRα signaling pathway in THP-1 macrophage-derived foam cells

脂氧素A4通过LXRα信号通路促进THP-1巨噬细胞衍生的泡沫细胞中ABCA1的表达和胆固醇外流

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作者:Yan-Hua Sha, Yan-Wei Hu, Ji-Juan Gao, Yan-Chao Wang, Xin Ma, Yu-Rong Qiu, Shu-Fen Li, Jia-Yi Zhao, Chuan Huang, Jing-Jing Zhao, Jing-Bo Lu, Chun-Min Kang, Lei Zheng, Qian Wang

Abstract

Adenosine triphosphate-binding cassette transporter A1 (ABCA1) is a crucial cholesterol transporter and plays a central role in the high density lipoproteins (HDL) cholesterol metabolism and lipid clearance from the foam cell. Lipoxin A4 (LXA4) is an endogenous lipid mediator that requires cell-cell interaction or cell-platelet interaction for its synthesis. The roles of LXA4 on inflammatory responses are well described, while its effects on mediating ABCA1 and underlying mechanisms remain unclear. In this study, we showed that LXA4 significantly increases expression of ABCA1 and LXRα in a dose-dependent manner in THP-1 macrophage-derived foam cells. Cellular cholesterol content was decreased while cholesterol efflux was increased by LXA4 treatment. However, after short interfering RNA of LXRα, the effects of LXA4 on ABCA1 expression and cholesterol metabolism were significantly abolished. These results provide evidence that LXA4 increases ABCA1 expression and promotes cholesterol efflux through LXRα pathway in THP-1 macrophage-derived foam cells.

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