Transcriptional repression of atherogenic inflammation: modulation by PPARdelta.

Science 2003 Oct 11;302(5644):453-7. Epub 2003 Sep 11.

Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

The formation of an atherosclerotic lesion is mediated by lipid-laden macrophages (foam cells), which also establish chronic inflammation associated with lesion progression. The peroxisome proliferator-activated receptor (PPAR) gamma promotes lipid uptake and efflux in these atherogenic cells. In contrast, we found that the closely related receptor PPARdelta controls the inflammatory status of the macrophage. Deletion of PPARdelta from foam cells increased the availability of inflammatory suppressors, which in turn reduced atherosclerotic lesion area by more than 50%. We propose an unconventional ligand-dependent transcriptional pathway in which PPARdelta controls an inflammatory switch through its association and disassociation with transcriptional repressors. PPARdelta and its ligands may thus serve as therapeutic targets to attenuate inflammation and slow the progression of atherosclerosis.

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.1087344DOI Listing
October 2003
4 Reads

Publication Analysis

Top Keywords

ppardelta controls
8
foam cells
8
controls inflammatory
8
atherosclerotic lesion
8
ppardelta
5
propose unconventional
4
lipid uptake
4
efflux atherogenic
4
uptake efflux
4
50% propose
4
promotes lipid
4
unconventional ligand-dependent
4
pathway ppardelta
4
proliferator-activated receptor
4
inflammatory switch
4
receptor ppar
4
transcriptional pathway
4
gamma promotes
4
ligand-dependent transcriptional
4
ppar gamma
4

Altmetric Statistics

Similar Publications