PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL

Peter Tontonoz, Laszlo Nagy, Jacqueline G.A. Alvarez, Vilmos A. Thomazy, Ronald M. Evans

Research output: Contribution to journalArticlepeer-review

1545 Scopus citations

Abstract

The formation of foam cells from macrophages in the arterial wall is characterized by dramatic changes in lipid metabolism, including increased expression of scavenger receptors and the uptake of oxidized low-density lipoprotein (oxLDL). We demonstrate here that the nuclear receptor PPARγ is induced in human monocytes following exposure to oxLDL and is expressed at high levels in the foam cells of atherosclerotic lesions. Ligand activation of the PPARγ:RXRα heteredimer in myelomonocytic cell lines induces changes characteristic of monocytic differentiation and promotes uptake of oxLDL through transcriptional induction of the scavenger receptor CD36. These results reveal a novel signaling pathway controlling differentiation and lipid metabolism in monocytic cells, and suggest that endogenous PPARγ ligands may be important regulators of gene expression during atherogenesis.

Original languageEnglish (US)
Pages (from-to)241-252
Number of pages12
JournalCell
Volume93
Issue number2
DOIs
StatePublished - Apr 17 1998
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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