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PMID: 9568716 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL.

Cell ·Vol. 93 ·No. 2 ·1998-04-17 ·Pages 241-52

Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM

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.

MeSH Terms

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

Chemicals

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

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Tontonoz P

The Salk Institute for Biological Studies, La Jolla, California 92037, USA.

Nagy L

Alvarez J G

Thomazy V A

Evans R M

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(00)81575-5

Published

1998-04-17

Pages

241-52

Language

English

Region

United States

NLM ID

0413066

Subset

External Links

PubMed source DOI: 10.1016/s0092-8674(00)81575-5 View journal details

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PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL.

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