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

Ajay Chawla, William A. Boisvert, Chih Hao Lee, Bryan A. Laffitte, Yaacov Barak, Sean B. Joseph, Debbie Liao, Laszlo Nagy, Peter A. Edwards, Linda K. Curtiss, Ronald M. Evans, Peter Tontonoz

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1031 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)161-171
Number of pages11
JournalMolecular Cell
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 1 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Chawla, A., Boisvert, W. A., Lee, C. H., Laffitte, B. A., Barak, Y., Joseph, S. B., Liao, D., Nagy, L., Edwards, P. A., Curtiss, L. K., Evans, R. M., & Tontonoz, P. (2001). A PPARγ-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Molecular Cell, 7(1), 161-171. https://doi.org/10.1016/S1097-2765(01)00164-2