Oxidized LDL regulates macrophage gene expression through ligand activation of PPARγ

Laszlo Nagy, Peter Tontonoz, Jacqueline G A Alvarez, Hongwu Chen, Ronald M. Evans

Research output: Contribution to journalArticle

1467 Scopus citations

Abstract

Macrophage uptake of oxidized low-density lipoprotein (oxLDL) is thought to play a central role in foam cell formation and the pathogenesis of atherosclerosis. We demonstrate here that oxLDL activates PPARγ-dependent transcription through a novel signaling pathway involving scavenger receptor- mediated particle uptake. Moreover, we identify two of the major oxidized lipid components of oxLDL, 9-HODE and 13-HODE, as endogenous activators and ligands of PPARγ. Our data suggest that the biologic effects of oxLDL are coordinated by two sets of receptors, one on the cell surface, which binds and internalizes the particle, and one in the nucleus, which is transcriptionally activated by its component lipids. These results suggest that PPARγ may be a key regulator of foam cell gene expression.

Original languageEnglish (US)
Pages (from-to)229-240
Number of pages12
JournalCell
Volume93
Issue number2
DOIs
StatePublished - Apr 17 1998
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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