Document Detail


PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL.
MedLine Citation:
PMID:  9568716     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
P Tontonoz; L Nagy; J G Alvarez; V A Thomazy; R M Evans
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell     Volume:  93     ISSN:  0092-8674     ISO Abbreviation:  Cell     Publication Date:  1998 Apr 
Date Detail:
Created Date:  1998-05-21     Completed Date:  1998-05-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  241-52     Citation Subset:  IM    
Affiliation:
The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD36 / analysis,  genetics
Arteriosclerosis / pathology
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
Scavenger Receptors, Class B
Signal Transduction / physiology
Thiazoles / pharmacology
Thiazolidinediones*
Transcription Factors / analysis,  chemistry,  metabolism,  physiology*
Transcriptional Activation / genetics,  physiology
Tretinoin / pharmacology
Chemical
Reg. No./Substance:
0/15-deoxy-delta(12,14)-prostaglandin J2; 0/Antigens, CD36; 0/Ligands; 0/Lipoproteins, LDL; 0/Membrane Proteins; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, Immunologic; 0/Receptors, Lipoprotein; 0/Receptors, Retinoic Acid; 0/Receptors, Scavenger; 0/Retinoid X Receptors; 0/Scarb1 protein, mouse; 0/Scavenger Receptors, Class B; 0/Thiazoles; 0/Thiazolidinediones; 0/Transcription Factors; 0/oxidized low density lipoprotein; 122320-73-4/rosiglitazone; 302-79-4/Tretinoin; 41598-07-6/Prostaglandin D2; 5300-03-8/alitretinoin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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