α2-Antiplasmin on Cardiovascular Diseases

Hiroyuki      Matsuno

doi:10.2174/138161206776056038

Abstract

Circumstantial evidence has been provided of a role of the plasminogen/plasmin system in a variety of biological phenomena, including thrombolysis, vascular stenosis, reproduction, embryogenesis, cell invasion, angiogenesis, brain function and chronic lung or kidney inflammatory disorders. Inhibition of the system occurs either at the levels of plasminogen activator, regulated by specific plasminogen activator inhibitors (PAIs) or at the levels of plasmin, mainly regulated by α2-antiplasmin (α2-AP). α2-AP is a specific plasmin inhibitor. We investigated the role of α2-AP on arterial or venous thrombus formation using mice deficient α2-AP and the interactions among lack of α2-AP, antiplatelet, anticoagulant and thrombolytic compounds were evaluated using murine thrombus model. These results clearly indicate that α2-AP plays a different role in acute arterial thrombosis or venous thrombosis. Additionally, lack of α2-AP significantly affected anti-coagulant and thrombolytic action, but not anti-platelet compounds, on the development of thrombus formation in vivo. Recent findings reported that plasmin cleaves vascular endothelial growth factor (VEGF) in extracellular matrix. Our findings newly indicate that lack of α2-AP enhances the secretion of VEGF in acute myocardial infarction and over secretion of VEGF promotes heart failure by pulmonary edema. Moreover, regulation of VEGF by α2-AP significantly affected reendothelialization after vascular injury. These findings indicate a potential new aspect in this field and could be a useful report for the development of novel antithrombotic compounds.

Keywords: vascular diseases, thrombolytic, VENOUS THROMBOSIS, vascular endothelial growth factor (VEGF), plasminogen activator inhibitors (PAIs)

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