Various reguratory mechanisms of activated-platelet' memberane-based activation of fibrinolysis.
| Project/Area Number |
16K08492
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 優子 浜松医科大学, 医学部, 准教授 (20345812)
岩城 孝行 浜松医科大学, 医学部, 准教授 (70509463)
佐野 秀人 浜松医科大学, 医学部, 助教 (80623842)
田中 宏樹 浜松医科大学, 医学部, 特任研究員 (50456563)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 線溶 / 血小板 / 凝固 / プラスミノゲン / トロンビン活性化線溶阻害因子 / プラスミノゲン アクチベータ / 血管内皮細胞 / TAFI / トロンボモジュリン / 血管内皮 / 血液凝固 / 血管愛内皮細胞 / 血栓溶解 / イメージング |
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| Outline of Final Research Achievements |
When platelet-rich plasma was treated by tissue factor and CaCl2, activated platelets initiated not only fibrin formation but also fibrinolysis after triggering the accumulation of both tissue plasminogen activator and plasminogen on their surfaces. The latter was attenuated by recombinant thrombomodulin, an essential cofactor for thrombin to activate thrombin activatable fibrinolysis inhibitor, which was reversed by either carboxypeptidase inhibitor or neutralizing antibody to block the interaction of thrombin and thrombomodulin. Activated platelets appeared not only to facilitate the activation of coagulation cascade but also to diversely regulate fibrinolysis.
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| Academic Significance and Societal Importance of the Research Achievements |
血栓形成は場所と時間で巧妙に調節されており、内皮障害部等の必要部位では迅速に形成されるが、正常内皮細胞の存在する不要部位では形成が抑制されたり形成されても速やかに溶解される機構がある。凝固系が活性化血小板上でだけ活性化されるのは前者に関わる。線溶系に対する血小板の影響は不明であったが、フィブリン形成の促進に伴い線溶が促進するという基本機構が存在すること、内因性あるいは外来性のトロンボモジュリンにより活性化される TAFI によりその基本機構が修飾され線溶阻害にも関わることが明らかになった。これらを修飾する薬剤により、より安全な抗凝固療法や血栓溶解療法の確立が期待される。
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] Elevated Plasma Levels of LDL Cholesterol Promote Dissecting Thoracic Aortic Aneurysms in Angiotensin II-Induced Mice.2018
Author(s)
Tanaka H, Iida Y, Iwaki T, Suzuki Y, Sano H, Miyajima C, Zaima N, Sasaki T, Sumioka A, Hakamata S, Shimizu H, Umemura K, Urano T.
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Journal Title
Ann Vasc Surg.
Volume: 48
Pages: 204-213
DOI
Related Report
Peer Reviewed
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[Journal Article] Global Public Awareness about Atrial Fibrillation.2018
Author(s)
Wendelboe, Raskob GE, Angchaisuksiri P, Blanco AN, ller H, Ddungu, H, Dvorak JD, Hunt BJ, Hylek EM, Kakkar A, Konstantinides SV, McCumber M, McLintock C, Urano T, Weitz J.
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Journal Title
Res Pract Thromb Haemost.
Volume: 2
Issue: 1
Pages: 49-57
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Lysophosphatidylcholine Acyltransferase-3 Expression Is Associated with Atherosclerosis Progression.2017
Author(s)
Tanaka H, Zaima N, Sasaki T, Yamamoto N, Inuzuka K, Yata T, Iwaki T, Umemura K, Sano H, Suzuki Y, Urano T, Setou M, Unno N
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Journal Title
J Vasc Res
Volume: 54(4)
Issue: 4
Pages: 200-208
DOI
Related Report
Peer Reviewed
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[Journal Article] Venous Thromboembolism: Assess the Risk and Reduce the Burden.2016
Author(s)
Raskob GE, Angchaisuksiri P, Blanco AN, Buller H, Ddungu H, Hunt BJ, Hylek EM, Kakkar A, Konstantinides SV, McCumber M, McLintock C, Urano T, Wendelboe A, Weitz JI
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Journal Title
Thrombosis and Haemostasis
Volume: 116
Issue: 11
Pages: 777-779
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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