Transcriptional Repression of Atherogenic Inflammation: Modulation by PPAR
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)
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.
Abstract/PDF