Review: Vascular protective effects of peroxisome proliferator-activated receptor agonists

Abstract

ardiovascular disease is significantly increased in patients with the metabolic syndrome and type 2 diabetes. A clustering of risk factors, including dyslipidaemia, insulin resistance, hypertension, inflammation and coagulation disorders are acting in concert to promote cardiovascular events in these patients. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that influence vascular function by altering gene expression in vascular tissue and indirectly via effects on other tissues. Indeed, PPAR activation displays beneficial effects on glucose homeostasis and lipid metabolism, and also on endothelial function and vessel wall inflammation. Clinically used PPARα agonists, such as fibrates, and PPARγ agonists, such as insulin-sensitising thiazolidinediones, may consequently alter the process of atherosclerosis, especially in subjects with the metabolic syndrome and type 2 diabetes. The present review highlights emerging evidence for beneficial effects of PPAR α and PPARγ in the prevention and treatment of atherosclerosis in such high-risk patients.