2004 Fiscal Year Final Research Report Summary
Identficatbn of roles and significance between plasmin and VEGF on regenerative medicine
| Project/Area Number |
15590223
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Gifu University |
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Principal Investigator |
MATSUNO Hiroyuki Gifu Univ., School of Med.Pharmacol., Associate prof., 大学院・医学研究科, 助教授 (40273148)
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| Co-Investigator(Kenkyū-buntansha) |
KOZAWA Osamu Gifu Univ., School of Med.Pharmacol., Prof., 大学院・医学研究科, 教授 (90225417)
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| Project Period (FY) |
2003 – 2004
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| Keywords | VEGF / Plamsin / Atherosclerosis / Endothelial cell / Regenerative medicine / Ischemia / Thrombosis |
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| Research Abstract |
Circumstantial evidence has been provided of a role of the plasminogen/plasmin system in a variety of biological phenomena jncluding thrembolysis, 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 inhbitors (PAls) or at the levels of plasmin, mainly regulated by a2-antiplasmin (a2-AP). 2-AP is a specific plasmin inhibitor. We investigated a role of a2-AP on arterial or venous thrombus formation using mice deficient a2-AP and the interactions among lack of a2-AP, antiplatelet, anticoagulant and thrombolytic compounds were evaluated using murine thrombus model. These results clearly indicate that a2-AP plays a different role in acute arterial thrombosis or venous thrombosis. Additionally, lack of a2-AP significantly affected anti-coagulant and thromboytic 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 extracefular matrix. Our findings newly indicate that lack of a2-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 a2-AP significantly affected reendothelialization after vascular injury. These findings indicate a potential new aspect in this filed and could be a useful report for the development of novel antithrombotic compounds.
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Research Products
(12 results)
