The effects of PPAR agonists on vascular biology and atherosclerosis are an obvious issue given the patient populations that receive these drugs. Thiazolidinediones are used in patients with DM, and thus in patients with well-defined increased risk for cardiovascular events (12). Fibrates are used to treat patients with increased triglycerides and low HDL, a profile with increased cardiovascular risk often seen among patients with insulin resistance if not frank diabetes (18). Theoretically, PPAR agonists could have vascular benefits based on their various metabolic effects—improving insulin sensitivity, lowering glucose, and raising HDL. An alternative but not mutually exclusive hypothesis would be that if PPARs are expressed in vascular and inflammatory cells, then PPAR agonists could have direct effects that might influence atherosclerosis (4). Indeed, this issue has become an area of considerable interest. All PPAR isoforms are now known to be expressed in endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and monocytes/macrophages and T-lymphocytes (28,29). An increasing amount of data continues to identify various PPAR-regulated target genes that are known to be involved in atherosclerosis. Moreover, this data is extending to in vivo studies in both rodents and humans.
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