Peroxisome proliferator-activated receptor-gamma agonists for management and prevention of vascular disease in patients with and without diabetes mellitus.

Inflammation is known to have a pathogenic role in atherosclerosis and the genesis of acute coronary syndromes. The peroxisome proliferator-activated receptor (PPAR)-gamma, which is expressed in many constituent cells of atheromatous plaques, inhibits the activation of several proinflammatory genes responsible for atheromatous plaque development and maturation. Agonists of this receptor, such as rosiglitazone and pioglitazone, are currently available for the treatment of type 2 diabetes mellitus, and several lines of evidence have shown that these drugs have antiatherogenic effects. Insulin resistance is associated with inflammation and has a key role in atherogenesis. The antiatherogenic and insulin sensitizing effects of the thiazolidinediones in patients with type 2 diabetes mellitus may be associated with this action. However, in recent years there has been growing evidence that the antiatherogenic effects of PPAR-gamma agonists are not confined to patients with diabetes mellitus. PPAR-gamma agonists have been shown to downregulate the expression of endothelial activation markers, reduce circulating platelet activity, improve flow-mediated dilatation and attenuate atheromatous plaque progression in patients without diabetes mellitus. These effects of PPAR-gamma agonists appear to result from both insulin sensitization and a direct modulation of transcriptional activity in the vessel wall. This review summarizes the current understanding of the role of PPAR-gamma agonists in atherogenesis and discusses their potential role in the treatment of coronary artery disease in patients with type 2 diabetes mellitus and in nondiabetic patients.