Alpha2-antiplasmin on cardiovascular diseases.
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 alpha2-antiplasmin (alpha2-AP). alpha2-AP is a specific plasmin inhibitor. We investigated the role of alpha2-AP on arterial or venous thrombus formation using mice deficient alpha2-AP and the interactions among lack of alpha2-AP, antiplatelet, anticoagulant and thrombolytic compounds were evaluated using murine thrombus model. These results clearly indicate that alpha2-AP plays a different role in acute arterial thrombosis or venous thrombosis. Additionally, lack of alpha2-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 alpha2-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 alpha2-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.
Matsuno
Hiroyuki
H
Department of Clinical Pathological Biochemistry, Doshisha Women's College of Liberal Arts, Kyo-tanabe, Kyoto 610-0395, Japan. hmatsuno@dwc.doshisha.ac.jp
D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000502:physiology*
D042461:Vascular Endothelial Growth Factor A; D000979:alpha-2-Antiplasmin