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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1310.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

LXR-Induced Redistribution of ABCG1 to Plasma Membrane in Macrophages Enhances Cholesterol Mass Efflux to HDL

Nan Wang; Mollie Ranalletta; Fumihiko Matsuura; Felix Peng; Alan R. Tall

From the Division of Molecular Medicine, Department of Medicine, Columbia University, New York.

Correspondence to Nan Wang, Division of Molecular Medicine, Department of Medicine, PS 8-401, Columbia University, 630 West 168th Street, New York, NY 10032. E-mail nw30{at}columbia.edu

Objectives— This study examines the ABCG1-mediated cholesterol efflux and intracellular cholesterol transport by studying the ABCG1 localization and function in macrophages.

Methods and Results— HEK 293 cell overexpressing ABCG1, RNA interference, or macrophages from ABCG1 or ABCG4 knockout mice were used. ABCG1 but not ABCG4 had a major role in the increased cholesterol mass efflux produced by treatment of macrophages with LXR activators. In 293 cells, ABCG1 was found in the plasma membrane, Golgi, and recycling endosomes. In contrast, in basal macrophages, ABCG1 was predominantly intracellular, and redistributed to the plasma membrane after LXR activation. LXR activation increased macrophage cholesterol efflux to high-density lipoprotein (HDL), low-density lipoprotein (LDL), and cyclodextrin in an ABCG1-dependent fashion. Suppression of ABCG1 expression increased cholesteryl ester formation and decreased SREBP2 target gene expression in macrophages, even in the absence of HDL acceptors.

Conclusions— LXR activation induces redistribution of ABCG1 from intracellular sites to the plasma membrane and increases cholesterol mass efflux to HDL in an ABCG1-dependent fashion. ABCG1 acts in the macrophage plasma membrane to increase the availability of cholesterol to a variety of lipoprotein and nonlipoprotein acceptors while limiting the accumulation of cholesterol in the endoplasmic reticulum.

This study showed that ABCG1 has a major role in macrophage cholesterol efflux stimulated by LXR activation. LXR activation also induces a parallel redistribution of ABCG1 from intracellular sites to the plasma membrane. ABCG1 appears to act in the plasma membrane to increase the availability of cholesterol to a variety of lipoprotein and nonlipoprotein acceptors while limiting the accumulation of cholesterol in the endoplasmic reticulum.

Key Words: ABCG1 • cholesterol efflux • high-density lipoprotein • liver X receptor • macrophage

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Insight Into ABCG1-Mediated Cholesterol Efflux

Jonathan D. Smith
Arterioscler. Thromb. Vasc. Biol. 2006 26: 1198-1200. [Full Text] [PDF]

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