Sci. Aging Knowl. Environ., 17 September 2003
Transcriptional Repression of Atherogenic Inflammation: Modulation by PPAR
Chih-Hao Lee, Ajay Chawla, Ned Urbiztondo, Debbie Liao, William A. Boisvert, and Ronald M. Evanshttp://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) promotes lipid uptake and efflux in these atherogenic cells. In contrast, we found that the closely related receptor PPAR controls the inflammatory status of the macrophage. Deletion of PPAR 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 controls an inflammatory switch through its association and disassociation with transcriptional repressors. PPAR and its ligands may thus serve as therapeutic targets to attenuate inflammation and slow the progression of atherosclerosis.
Science of Aging Knowledge Environment. ISSN 1539-6150