Role of PPARgamma in macrophage biology and atherosclerosis.

Macrophages carry out key functions by defending a host from microbial invaders and by clearing endogenous cellular debris. Molecules that are essential for the recognition, phagocytosis and clearance of pathogens also mediate the uptake and degradation of pathogenic lipoproteins. During atherogenesis, for example, scavenging trapped lipoproteins leads to the formation of foam cells and subsequently the activation of these lipid-laden macrophages. Although they are initially clinically silent, these fatty streaks evolve into complex inflammatory plaques that cause significant morbidity and mortality. Thus, interventions that decrease foam cell formation and reduce the inflammatory response of macrophages could become effective therapies for coronary artery disease. Thiazolidinediones (TZDs) might be developed as anti-atherogenic agents on the basis of their actions as ligands for peroxisome proliferator-activated receptor-gamma (PPARgamma).