Transcriptional repression of atherogenic inflammation: modulation by PPARdelta - PubMed (original) (raw)

. 2003 Oct 17;302(5644):453-7.

doi: 10.1126/science.1087344. Epub 2003 Sep 11.

Affiliations

• PMID: 12970571
• DOI: 10.1126/science.1087344

Transcriptional repression of atherogenic inflammation: modulation by PPARdelta

Chih-Hao Lee et al. Science. 2003.

Erratum in

• Science. 2003 Nov 14;302(5648):1153

Abstract

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.

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Comment in

• Medicine. PPARs as therapeutic targets: reverse cardiology?
  Plutzky J. Plutzky J. Science. 2003 Oct 17;302(5644):406-7. doi: 10.1126/science.1091172. Science. 2003. PMID: 14563997

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