Transcriptional Repression of Atherogenic Inflammation: Modulation by PPAR{delta}

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Sci. Aging Knowl. Environ., 17 September 2003
Vol. 2003, Issue 37, p. or16

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Transcriptional Repression of Atherogenic Inflammation: Modulation by PPAR ${delta}$

Chih-Hao Lee, Ajay Chawla, Ned Urbiztondo, Debbie Liao, William A. Boisvert, and Ronald M. Evans

http://sageke.sciencemag.org/cgi/content/abstract/sageke;2003/37/or16

Abstract: Science 11 September 2003 (10.1126/science.1087344) (Science Express Reports)

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 PPAR ${delta}$ controls the inflammatory status of the macrophage. Deletion of PPAR ${delta}$ from foam cells increased the availability of inflammatory suppressors, which in turn reduced atherosclerotic lesion by more than 50%. We propose an unconventional ligand-dependent transcriptional pathway in which PPAR ${delta}$ controls an inflammatory switch through its association and disassociation with transcriptional repressors. PPAR ${delta}$ and its ligands may thus serve as therapeutic targets to attenuate inflammation and slow the progression of atherosclerosis.