Pioglitazone and mechanisms of CV protection.
OBJECTIVE
Pioglitazone has diverse multiple effects on metabolic and inflammatory processes that have the potential to influence cardiovascular disease pathophysiology at various points in the disease process, including atherogenesis, plaque inflammation, plaque rupture, haemostatic disturbances and microangiopathy.


RESULTS
Linking the many direct and indirect effects on the vasculature to the reduction in key macrovascular outcomes reported with pioglitazone in patients with type 2 diabetes presents a considerable challenge. However, recent large-scale clinical cardiovascular imaging studies are beginning to provide some mechanistic insights, including a potentially important role for improvements in high-density lipoprotein cholesterol with pioglitazone. In addition to a role in prevention, animal studies also suggest that pioglitazone may minimize damage and improve recovery during and after ischaemic cardio- and cerebrovascular events.


METHODS
In this review, we consider potential cardiovascular protective mechanisms of pioglitazone by linking preclinical data and clinical cardiovascular outcomes guided by insights from recent imaging studies.


CONCLUSIONS
Pioglitazone may influence CVD pathophysiology at multiple points in the disease process, including atherogenesis, plaque inflammation, plaque rupture and haemostatic disturbances (i.e. thrombus/embolism formation), as well as microangiopathy.
Erdmann
E
E
Department of Medicine, Heart Center, University of Cologne, Cologne, Germany. erland.erdmann@uni-koeln.de
Wilcox
R
R
D050197:Atherosclerosis / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000517:prevention & control; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000517:prevention & control; D007333:Insulin Resistance / Q000502:physiology; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D008076:Cholesterol, HDL; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone