Fibrinolysis and diabetic vascular disease: roles of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor

Diabetes is a major risk factor for cardiovascular morbidity and mortality, and is associated with poorer outcomes after acute coronary syndromes. Patients with Type 2 diabetes have a two- to fourfold higher risk of cardiovascular disease, compared with nondiabetics. Hypercoagulation and impaired fibrinolysis can lead to excessive fibrin accumulation within vessels, and in patients with Type 2 diabetes they can result in the onset of thrombosis. Impaired fibrinolysis may be induced by elevated plasma concentrations of plasminogen activator inhibitor (PAI)-1 or thrombin-activatable fibrinolysis inhibitor (TAFI), both potent inhibitors of fibrinolysis. Elevated plasma PAI-1 is strongly associated with insulin resistance and obesity, while elevated plasma TAR may be associated with hypercholesterolemia rather than insulin resistance. Therefore, medications that ameliorate impaired fibrinolysis by decreasing PAI-1 and TAR concentrations may reduce an increased risk of cardiovascular disease. This review highlights the way in which PAI-1 and TAR contribute to the impaired fibrinolysis and atherothrombosis that is seen in patients with Type 2 diabetes.