A PPARγ-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis

被引：1230

作者：

Chawla, A

Boisvert, WA

Lee, CH

Laffitte, BA

Barak, Y

Joseph, SB

Liao, D

Nagy, L

Edwards, PA

Curtiss, LK

Evans, RM

Tontonoz, P ^{[1
]}

机构：

[1] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA

[2] Univ Calif San Diego, Div Endocrinol & Metab, La Jolla, CA 92093 USA

[3] Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Biol Chem & Med, Los Angeles, CA 90095 USA

[5] Univ Debrecen, Med & Hlth Sci Ctr, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary

[6] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA

[7] Scripps Res Inst, Dept Vasc Biol, La Jolla, CA 92037 USA

来源：

MOLECULAR CELL | 2001年 / 7卷 / 01期

关键词：

D O I：

10.1016/S1097-2765(01)00164-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Previous work has implicated PPAR gamma in the regulation of CD36 expression and macrophage uptake of oxidized LDL (oxLDL). We provide evidence here that in addition to lipid uptake, PPAR gamma regulates a pathway of cholesterol efflux. PPAR gamma induces ABCA1 expression and cholesterol removal from macrophages through a transcriptional cascade mediated by the nuclear receptor LXR alpha. Ligand activation of PPAR gamma leads to primary induction of LXR alpha and to coupled induction of ABCA1. Transplantation of PPAR gamma null bone marrow into LDLR -/- mice results in a significant increase in atherosclerosis, consistent with the hypothesis that regulation of LXR alpha and ABCA1 expression is protective in vivo. Thus, we propose that PPAR gamma coordinates a complex physiologic response to oxLDL that involves particle uptake, processing, and cholesterol removal through ABCA1.

引用

页码：161 / 171

页数：11

共 35 条

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