Atherosclerotic inflammatory switch

The progression of an atherosclerotic lesion involves lipid-laden macrophages (foam cells) migrating to vascular lesion sites, where they elicit a chronic inflammatory response. Despite some progress in understanding the molecular mechanisms of macrophage lipid loading, the mechanisms that control macrophage inflammatory status have been unclear. In the September 11 Sciencexpress, Chih-Hao Lee and colleagues at the Salk Institute for Biological Studies show that peroxisome proliferator–activated receptor δ(PPARδ) controls an inflammatory switch in the macrophages involved in the atherosclerotic lesion (Sciencexpress, DOI:10.1126/science.1087344, September 11, 2003).

Lee et al. examined peritoneal macrophages in mice lacking the low-density lipoprotein receptor (LDLR-/-) transplanted with PPARδ-/- bone marrow. They observed that deletion of PPARδ from foam cells increased the availability of inflammatory suppressors, which in turn reduced the atherosclerotic lesion by more than 50%.

"We propose an unconventional ligand-dependent transcriptional pathway in which PPARδ controls an inflammatory switch through its association and disassociation with transcriptional ...