Pleiotropic vascular effects of PPARgamma ligands.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands have been used for several years as modulators of insulin sensitivity and glucose metabolism. Recent data from numerous studies have shown that PPARgamma ligands have numerous beneficial effects in the vasculature. They have been shown to regulate proliferation and migration of vascular smooth muscle cells as well as improving endothelial cell function. They improve blood pressure by actions at the resistance arteries and kidneys. Clinical trials have indicated that PPARgamma ligands can minimize the development of atherosclerosis as well as regulating other vascular inflammation. PPARgamma has been detected in all the cells found in the vessel wall as well as those cells associated with vascular pathophysiologies. In the monocyte/macrophage, PPARgamma ligands downregulate production of inflammatory cytokines and migration. Also, PPARgamma ligands regulate the expression of SR-A and CD36 receptors that take up lipids in the macrophage. PPARgamma has also been demonstrated to act through the liver X receptor alpha to increase the activity of reverse cholesterol transport in these cells. In dendritic cells and T-cells, PPARgamma ligands have been shown to inhibit activation and the initiation of inflammation. Inflammatory cytokines are downregulated in animal models administered PPARgamma ligands, leading to decreased atherosclerosis. While PPARgamma ligands have been useful in the treatment of type 2 diabetes, the important vasculoprotection elicited by these compounds could prove to be of greater benefit in the future.
Collins
Alan R
AR
Division of Endocrinology, Diabetes and Hypertension, The David Geffen School of Medicine, UCLA, Los Angeles, California 90095-7073, USA. acollins@mednet.ucla.edu
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D007333:Insulin Resistance; D008024:Ligands; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors