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The mechanism of platelet thrombus formation at site of endothelial damage under blood flow conditions

Research Project

Project/Area Number 13670744
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionTokai University

Principal Investigator

GOTO Shinya  Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (50225653)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥2,900,000 (Direct Cost: ¥2,900,000)
Keywordsthrombi / platelet / von Willebrand factor / laser confocal microscopy / collagen / matrix / P-selectin / 白血球 / 血流 / 血管内皮
Research Abstract

We investigated the mechanism of platelet thrombus formation at site of functional or mechanical damage of endothelial cells. When blood was perfused on the subendothelial matrix exposed at the site of endoihelial injury, platelets were activated upon interaction with the matrix under blood flow condition. The interaction between von Willebrand factor and its corresponding platelet receptor of glycoprotein (GP) Ibα in addition to the interaction between collagen and GP VI are two most important interaction necessary for platelet activation. The amount of platelets accumulated on the matrix surface increased when stent was placed and blood flow conditions were disturbed.
On the cultured endothelial cell surface, it is hard to visualize platelets interacting with endothelial cells even after full activation of them by cytokines. Tissue factor generated from endothelial cells play important roles on the enhancement of platelet thrombi, while it did not directly interact with platelet under blood flow conditions.
In conclusion, our newly developed imaging system enabled by ultra-fast laser confocal microscopy was useful to dissect the mechanism of platelet thrombus formation under blood flow conditions.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Shinya Goto: "Involvement of Glycoprotein VI in Platelet Thrombus Formation on both Collagen and von Willebrand Factor Surface under Blood Flow Conditions"Circulation. 106. 266-272 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shinya Goto: "Functional Significance of Adenosine 5-Diphosphate Receptor in Platelet Activation Initiated by Binding of von Willebrand Factor to Platelet GP Ibalpha Induced by Conditions of High Shear Rate"Circulation. 105. 2531-2536 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakakibara M: "Application of ex vivo Flow Chamber System for Assessment of Stent Thrombosis"Arteriosclerosis, Thrombosis and Vascular Biology. 22. 1360-1364 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Goto S: "Effect of Adenosine 5'-Diphosphate (ADP) Receptor Blockade on Platelet Aggregation under Flow"Blood. 99. 4644-4644 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida M: "Shear-Induced von Willebrand Factor-Mediated Platelet Surface Translocation of the CD40 Ligand"Thrombosis Research. (発売予定)(未定). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 後藤信哉: "動脈硬化の発症と進展に関与する血小板と白血球の相互作用の分子機構-血流条件下の検討-"分子循環器研究講演会講演記録集. 9. 31-33 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Goto S: "Effects of ticlopidine on von Willebrand factor-mediated shear-induced platelet activation and aggregation"Platelet. 12. 406-414 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li M: "Specific inhibiting characterization of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine "Chuanxiong", on platelet thrombus formation under high shear rates"Thrombosis Research. 104. 15-28 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 榊原守: "ステント周囲の血小板集積に影響を与える因子に関する検討"日本冠疾患学会雑誌. 7. 73-78 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Goto S, et al.: "Involvement of Glycoprotein VI in Platelet Thrombus Formation on both Collagen and von Willebrand Factor Surface under Blood Flow Conditions"Circulation. 106. 266-272 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Goto S, et al.: "Functional significance of adenosine 5'-diphosphate receptor (P2Y12) in platelet activation initiated by binding of von Willebrand factor to platelet GP Ibalpha induced by condition of high shear rate"Circulation. 105. 2531-2536 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakakibara M, et al.: "Application of ex vivo Flow Chamber System for the Assessment of Stent Thrombosis"Arteriosclerosis, Thrombosis, and Vascular Biology. 22. 1360-1364 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Goto S, et al.: "Effects of adenosine 5'-diphosphate (ADP) receptor blockade on platelet aggregation under flow"Blood. 99. 4644-464 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Goto S, et al.: "Interaction between platelet and leukocytes. Possible Roles in Atherosclerosis (in Japanese)"Proceedings of the Forum on the Molecular Cardiology. 9. 31-33 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida M, et al.: "Shear-Induced von Willebrand Factor-Mediated Platelet Surface Translocation of the CD40 Ligand"Thrombosis Research. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Goto S, et al.: "Effects of ticlopidine on von Willebrand factor-mediated shear-induced platelet activation and aggregation"Platelets.. 12. 406-414 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li M, et al.: "Specific inhibiting characterization of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine "Chuanxiong", on platelet thrombus formation under high shear rates"Throm Res. 104. 15-28 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakakibara M, et al.: "Factors influencing platelet accumulation around stents"Japanese Journal of Coronary Artery Disease. 7. 73-78 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shinya Goto: "Involvement of Glycoprotein VI in Platelet Thrombus Formation on both Collagen and von Willebrand Factor Surface under Blood Flow Conditions"Circulation. 106. 266-272 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinya Goto: "Functional Significance of Adenosine 5-Diphosphate Receptor in Platelet Activation Initiated by Binding of von Willebrand Factor to Platelet GP lblpha Induced by Conditions of High Shear Rate"Circulation. 105. 2531-2536 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakakibara M: "Application of ex vivo Flow Chamber System for Assessment of Stent Thrombosis"Arteriosclerosis, Thrombosis and Vascular Biology. 22. 1360-1364 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Goto S: "Effect of Adenosine 5'-Diphosphate(ADP)Receptor Blockade on Platelet Aggregation under Flow"Blood. 99. 4644-4644 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida M: "Shear -Induced von VVillebrand Factor-Mediated Platelet Surface Translocation of the CD40 Ligand"Thrombosis Research. (発表予定). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 後藤信哉: "動脈硬化の発症と進展に関与する血小板と白血球の相互作用の分子機構-血流条件下の検討-"分子循環器研究講演会講演記録集. 9. 31-33 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakakibara M: "Application of ex vivo Flow Chamber System for the Assessment of Stent Thrombosis"Arteriosclerosis,Thrombosis,and Vascular Biology. (発表予定). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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