PPARgamma Promotes monocyte/macrophage Differentiation and Uptake of Oxidized LDL

Cell. 1998 Apr 17;93(2):241-52. doi: 10.1016/s0092-8674(00)81575-5.

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 PPARgamma 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 PPARgamma:RXRalpha heterodimer 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 PPARgamma ligands may be important regulators of gene expression during atherogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alitretinoin
  • Animals
  • Arteriosclerosis / pathology
  • CD36 Antigens / analysis
  • CD36 Antigens / genetics
  • Cell Differentiation
  • Dimerization
  • Foam Cells / chemistry
  • HL-60 Cells
  • Humans
  • Ligands
  • Lipoproteins, LDL / metabolism*
  • Macrophages / chemistry
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Membrane Proteins*
  • Mice
  • Mice, Transgenic
  • Monocytes / chemistry
  • Monocytes / cytology*
  • Monocytes / metabolism*
  • Promoter Regions, Genetic / genetics
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / pharmacology
  • Receptors, Cytoplasmic and Nuclear / analysis
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Immunologic / genetics
  • Receptors, Lipoprotein*
  • Receptors, Retinoic Acid / chemistry
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Scavenger
  • Retinoid X Receptors
  • Rosiglitazone
  • Scavenger Receptors, Class B
  • Signal Transduction / physiology
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / analysis
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transcriptional Activation / genetics
  • Transcriptional Activation / physiology
  • Tretinoin / pharmacology

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • CD36 Antigens
  • Ligands
  • Lipoproteins, LDL
  • Membrane Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Immunologic
  • Receptors, Lipoprotein
  • Receptors, Retinoic Acid
  • Receptors, Scavenger
  • Retinoid X Receptors
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • oxidized low density lipoprotein
  • Rosiglitazone
  • Alitretinoin
  • Tretinoin
  • Prostaglandin D2