Published online before print October 30, 2003, doi: 10.1161/01.ATV.0000103951.67680.B1
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© 2004 American Heart Association, Inc.
Brief Reviews |
Decoding Transcriptional Programs Regulated by PPARs and LXRs in the Macrophage
Effects on Lipid Homeostasis, Inflammation, and Atherosclerosis
From the Department of Cellular and Molecular Medicine, Department of Medicine, University of California, San Diego, Calif.
Correspondence to Christopher K. Glass, Department of Cellular and Molecular Medicine, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651. E-mail cglass{at}ucsd.edu
Series Editor: James Scott
ATVB In Focus Lipoproteins, Inflammation, and Atherosclerosis
Previous Brief Reviews in this Series:
•Pennachhio LA, Rubin EM. Apolipoprotein A5, a newly identified gene that affects plasma triglyceride levels in humans and mice. 2003;23:529–534.
•Cullen P, Baetta R, Bellosta S, Bernini F, Chinetti G, Cignarella A, von Eckardstein A, Exley A, Goddard M, Hofker M, Hurt-Camejo E, Kanters E, Kovanen P, Lorkowski S, McPheat W, Pentikäinen M, Rauterberg J, Ritchie A, Staels B, Weitkamp B, de Winther M for the MAFAPS Consortium. Rupture of the atherosclerotic plaque: does a good animal model exist? 2003;23:535–542.
•Allayee H, Ghazalpour A, Lusis AJ. Using mice to dissect genetic factors in atherosclerosis. 2003;23:1501–1509.
•Calabresi L, Gomaraschi M, Franceschini G. Endothelial protection by high-density lipoproteins: from bench to bedside. 2003;23:1724–1731.
•Trigatti BL, Krieger M, Rigotti A. Influence of the MDL receptor SR-BI on lipoprotein metabolism and atherosclerosis. 2003;23:1732–1738.
Macrophages play essential roles in immunity and homeostasis. As professional scavengers, macrophages phagocytose microbes and apoptotic and necrotic cells and take up modified lipoprotein particles. These functions require tightly regulated mechanisms for the processing and disposal of cellular lipids. Under pathological conditions, arterial wall macrophages become foam cells by accumulating large amounts of cholesterol, contributing to the development of atherosclerosis. Peroxisome proliferator–activated receptors (PPARs) and liver X receptors (LXRs) are members of the nuclear receptor superfamily of transcription factors that have emerged as key regulators of macrophage homeostasis. PPARs and LXRs control transcriptional programs involved in processes of lipid uptake and efflux, lipogenesis, and lipoprotein metabolism. In addition, PPARs and LXRs negatively regulate transcriptional programs involved in the development of inflammatory responses. This review summarizes recent efforts to decode the differential and overlapping roles of PPARs and LXRs in the context of macrophage lipid homeostasis and the control of inflammation.
Key Words: peroxisome proliferator–activated receptor • liver X receptor • macrophage • lipid homeostasis • inflammation • atherosclerosis
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