title: Peroxisome proliferator-activated receptor-gamma agonists in atherosclerosis: current evidence and future directions.
abstract: OBJECTIVE
  The prevalence of type 2 diabetes globally is reaching epidemic proportions. Type 2 diabetes is strongly associated with increased risk of cardiovascular disease. Atherosclerosis is thought to arise as a result of a chronic inflammatory process within the arterial wall. Insulin resistance is central to the pathogenesis of type 2 diabetes and may contribute to atherogenesis, either directly or through associated risk factors. The peroxisome proliferator-activated receptor-gamma agonists, the thiazolidinediones, pioglitazone and rosiglitazone, are insulin sensitizing agents, that are licensed for the management of hyperglycaemia. Growing evidence supports an array of additional effects of thiazolidinedione therapy, both immunomodulatory and antiinflammatory, which may attenuate atherogenesis in type 2 diabetes.
  
  
  RESULTS
  Studies have shown that thiazolidinedione therapy may lead to risk factor modulation in type 2 diabetes. Thiazolidinediones treatment has been shown to reduce blood pressure, modify the atherogenic lipid profile associated with type 2 diabetes, reduce microalbuminuria and ameliorate the prothrombotic diathesis. Further evidence suggests that thiazolidinediones therapy inhibits the inflammatory processes which may be involved in atherosclerotic plaque initiation, propagation and destabilization.
  
  
  CONCLUSIONS
  Modification of insulin resistance by thiazolidinedione therapy in type 2 diabetes and the range of pleiotropic effects may not only impact on incident type 2 diabetes, but also on associated cardiovascular disease. Numerous large clinical endpoint studies are under way to investigate these issues.
authors: Department of Metabolic Medicine, University Hospital of Wales and School of Biomedical Sciences, University of Wales Institute Cardiff, Cardiff, Wales, UK.
authors: Aled W
authors: AW
authors: Roberts
authors: Andrew
authors: A
authors: Thomas
authors: Alan
authors: A
authors: Rees
authors: Marc
authors: M
authors: Evans
mesh_terms: D000419:Albuminuria / Q000188:drug therapy; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000187:drug effects; D023903:Coronary Restenosis / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007333:Insulin Resistance / Q000502:physiology; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D047495:PPAR gamma / Q000819:agonists* / Q000502:physiology; D000077205:Pioglitazone; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D019332:Endothelin-1; D008074:Lipoproteins; D047495:PPAR gamma; D017395:Plasminogen Activator Inhibitor 1; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002097:C-Reactive Protein; D008687:Metformin; D020782:Matrix Metalloproteinases; D000077205:Pioglitazone