Peroxisome proliferator-activated receptors and the vascular system: beyond their metabolic effects

Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are ligand-activated transcription factors belonging to the nuclear receptor superfamily. PPARalpha has effects on fatty acid metabolism and its activation by fibrates results in reduction of triglyceride concentrations in blood. PPARgamma induces differentiation of adipocytes, and its activation by thiazolidinediones (TZDs) has insulin sensitizing effects, for which reason these agents are used for treating type 2 diabetes. PPARalpha and PPARgamma are present in the vasculature, where they have been shown to exert antioxidant and anti-inflammatory effects and to blunt the development of fibrosis and remodeling in experimental models and in several cardiovascular clinical conditions. This review will discuss some of the evidence, both experimental and clinical, that suggests that activation of PPARalpha and PPARgamma in hypertension may exert beneficial cardiovascular protective effects. However, a recent meta-analysis suggests an excess of myocardial infarction and borderline excess of cardiovascular death in type 2 diabetic patients treated with rosiglitazone. Thus the safety of use of PPARgamma activators for cardiovascular prevention and whether they are protective or actually may be harmful remains to be established.