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Understanding in spatio-temporal regulation mechanism of thrombus formation and dissolution for realization of appropriate antithrombotic therapy

Research Project

Project/Area Number 19K08577
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Suzuki Yuko  浜松医科大学, 医学部, 教授 (20345812)

Co-Investigator(Kenkyū-buntansha) 浦野 哲盟  浜松医科大学, 医学部, 特命研究教授 (50193967)
佐野 秀人  浜松医科大学, 医学部, 助教 (80623842)
本藏 直樹  浜松医科大学, 医学部, 准教授 (40518081)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords線維素溶解(線溶) / 可視化解析 / 血小板 / 血栓形成 / トロンビン生成 / トロンボモジュリン / トロンビン活性化線溶抑制因子 / 蛍光顕微鏡 / 線溶反応 / 活性化血小板 / トロンビン活性 / プラスミノゲン集積 / 直接経口抗凝固薬 / 線溶 / 血栓形成溶解 / 時空間的制御機構 / リアルタイムイメージング解析 / 疑似血管モデル / 抗血栓療法
Outline of Research at the Start

心筋梗塞、脳梗塞等の血栓性疾患に対する薬物療法では抗血小板薬や抗凝固薬、さらに発症直後には血栓溶解薬が用いられるが、一方でその副作用として出血性リスクの上昇に伴う生命予後の悪化が問題となっている。本研究では止血血栓形成能を維持し、かつ十分な血管内血栓形成抑制効果が期待できるような薬物療法の確立を目指して、時空間的に巧妙に増幅制御された「血栓形成-溶解連関」を解明することを目的とする。

Outline of Final Research Achievements

The blood coagulation system is precisely regulated by either facilitating the activation of its cascade, resulting in prompt hemostatic thrombus formation at the vascular injury site, or preventing thrombus formation by inhibiting their activation in the vessels. It is well known that intravascular thrombus forms easily in various pathological conditions such as atherosclerosis, lifestyle-related disease, and aging, including atrium fibrillation. Antithrombotic drugs, either used for prophylactic or treatment in thrombotic patients, suppress hemostatic thrombus formation but increase the risk of bleeding. Therefore, the formation and dissolution of a thrombus should be clearly explained to deal with such a problem. This study investigated the formation and dissolution of a thrombus by directly visualizing the process using fluorescence microscopy. As a result, we expect the possibility of an effective treatment for thrombosis that reduces the risk of bleeding.

Academic Significance and Societal Importance of the Research Achievements

心筋梗塞や脳梗塞をはじめとした従来の血栓性疾患のみならず、近年では新型コロナウイルス感染症の重症化ならびにワクチン接種における血栓症リスクがクローズアップされた。本研究では血小板の活性化、凝固反応の活性化、生じた血栓を溶かす線維素溶解(線溶)の各反応系を一連の時空間的に制御される反応系として解析した。これをさらに各病態に応じた反応系として捉えることで、より適切な血栓症の治療・予防法の確立につながることが期待できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (26 results)

All 2022 2021 2020 2019

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (15 results) (of which Int'l Joint Research: 5 results,  Invited: 6 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Pre-administration of a carboxypeptidase inhibitor enhances tPA-induced thrombolysis in mouse microthrombi: Evidence from intravital imaging analysis2022

    • Author(s)
      Mathews Nitty Skariah、Suzuki Yuko、Honkura Naoki、Sano Hideto、Iwashita Toshihide、Urano Tetsumei
    • Journal Title

      Thrombosis Research

      Volume: 210 Pages: 78-86

    • DOI

      10.1016/j.thromres.2021.12.031

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Demonstration of Three Distinct High-Molecular-Weight Complexes between Plasminogen Activator Inhibitor Type 1 and Tissue-Type Plasminogen Activator2021

    • Author(s)
      Ito Tae、Suzuki Yuko、Sano Hideto、Honkura Naoki、Castellino Francis J.、Urano Tetsumei
    • Journal Title

      Thrombosis and Haemostasis

      Volume: 122 Issue: 03 Pages: 336-343

    • DOI

      10.1055/a-1508-7919

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] リアルタイムイメージング技術が照らす線溶反応の時空間的制御機構2021

    • Author(s)
      鈴木優子
    • Journal Title

      日本血栓止血学会誌

      Volume: 32 Pages: 495-503

    • NAID

      130008080757

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Activated platelet-based inhibition of fibrinolysis via thrombin-activatable fibrinolysis inhibitor activation system2020

    • Author(s)
      Suzuki Yuko、Sano Hideto、Mochizuki Liina、Honkura Naoki、Urano Tetsumei
    • Journal Title

      Blood Advances

      Volume: 4 Issue: 21 Pages: 5501-5511

    • DOI

      10.1182/bloodadvances.2020002923

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fibrinolysis-resistant carbonylated fibrin detected in thrombi attached to the vascular wall of abdominal aortic aneurysms2020

    • Author(s)
      Suzuki Yuko、Tanaka Hiroki、Horinouchi Takahiro、Sano Hideto、Honkura Naoki、Unno Naoki、Miwa Soichi、Urano Tetsumei
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 20728-20728

    • DOI

      10.1038/s41598-020-77582-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spatiotemporal regulation of thrombus formation and dissolution2020

    • Author(s)
      鈴木 優子、浦野 哲盟
    • Journal Title

      Rinsho Ketsueki

      Volume: 61 Issue: 9 Pages: 1349-1357

    • DOI

      10.11406/rinketsu.61.1349

    • NAID

      130007937061

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2020 Research-status Report
  • [Journal Article] The Role of Animal Models in Elucidating the Etiology and Pathology of Abdominal Aortic Aneurysms: Development of a Novel Rupture Mechanism Model2020

    • Author(s)
      Tanaka Hiroki、Zaima Nobuhiro、Kugo Hirona、Yata Tatsuro、Iida Yasunori、Hashimoto Keisuke、Miyamoto Chie、Sasaki Takeshi、Sano Hideto、Suzuki Yuko、Moriyama Tatsuya、Shimizu Hideyuki、Inuzuka Kazunori、Urano Tetsumei、Unno Naoki
    • Journal Title

      Annals of Vascular Surgery

      Volume: 63 Pages: 382-390

    • DOI

      10.1016/j.avsg.2019.08.082

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessing plasminogen activation potential with global fibrinolytic assays2019

    • Author(s)
      Urano Tetsumei、Suzuki Yuko
    • Journal Title

      Research and Practice in Thrombosis and Haemostasis

      Volume: 4 Issue: 1 Pages: 13-15

    • DOI

      10.1002/rth2.12293

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recognition of Plasminogen Activator Inhibitor Type 1 as the Primary Regulator of Fibrinolysis2019

    • Author(s)
      Urano T, Suzuki Y, Iwaki T, Sano H, Honkura N, Castellino FJ.
    • Journal Title

      Curr Drug Targets.

      Volume: 20 Issue: 16 Pages: 1695-1701

    • DOI

      10.2174/1389450120666190715102510

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] G-protein-coupled receptor 40 agonist GW9508 potentiates glucose-stimulated insulin secretion through activation of protein kinase Cα and ε in INS-1 cells2019

    • Author(s)
      Hashimoto Takuya、Mogami Hideo、Tsuriya Daisuke、Morita Hiroshi、Sasaki Shigekazu、Kumada Tatsuro、Suzuki Yuko、Urano Tetsumei、Oki Yutaka、Suda Takafumi
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 9 Pages: e0222179-e0222179

    • DOI

      10.1371/journal.pone.0222179

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Imaging analysis of cell-based regulation of fibrinolysis2022

    • Author(s)
      Yuko Suzuki, Tetsumei Uranno
    • Organizer
      The 3rd Joint Meeting of the International Society of Fibrinolysis and Proteolysis and the Plasminogen Activation Workshop
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Spatiotemporal regulation of TAFI activation, plasminogen activation, and fibrinolysis by thrombin2022

    • Author(s)
      Yuko Suzuki
    • Organizer
      2022 Gordon Research Conference (GRC) on Plasminogen Activation and Extracellular Proteolysis
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生体顕微鏡を用いたレーザ惹起微小血栓溶解におけるcarboxypeptidase inhibitorの効果2022

    • Author(s)
      鈴木優子、Nitty Mathws、佐野秀人、本藏直樹、浦野哲盟
    • Organizer
      第44回日本血栓止血学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Real time imaging techniques illminate spatiotemporal regulation of fibrinolysis2021

    • Author(s)
      鈴木優子
    • Organizer
      第43回日本血栓止血学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Spatiotemporal regulation of fibrinolysis via thrombomodulin/thrombin/ TAFI system.2021

    • Author(s)
      2.Yuko Suzuki, Hideto Sano, Naoki Honkura, Tetsumei Urano
    • Organizer
      第43回日本血栓止血学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 活性化血小板による線維素溶解(線溶)抑制機構2021

    • Author(s)
      鈴木優子、望月里衣奈、佐野秀人、本藏直樹、浦野哲盟
    • Organizer
      第68回中部日本生理学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 「教育講演」血栓形成溶解の時空間的制御2020

    • Author(s)
      鈴木 優子
    • Organizer
      第82回日本血液学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 特別企画シンポジウム「次世代リーダーからのメッセージ」血栓形成-溶解機構の時空間的解析2020

    • Author(s)
      鈴木 優子
    • Organizer
      第42回日本血栓止血学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Modulation of thrombin generation or thrombin activity on activated platelets surface largely affected TAFI-dependent regulation of fibrinolysis.2020

    • Author(s)
      Suzuki Y, Sano H, Honkura N, Urano T
    • Organizer
      The XXVII Congress of the International Society on Thrombosis and Hemostasis (ISTH),
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] トロンビンによるTAFIの活性化を介した線溶阻害作用のリアルタイムイメージング解析2020

    • Author(s)
      鈴木 優子,佐野 秀人, 本藏 直樹, 浦野 哲盟
    • Organizer
      第82回日本血液学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Spatiotemporal regulation of thrombin-activatable fibrinolysis inhibitor (TAFI) activation on activated platelets2020

    • Author(s)
      Yuko Suzuki
    • Organizer
      Gordon Research Conference; Plasminogen Activation and Extracellular Proteolysis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血栓形成と溶解反応におけるクロストークの時空間的解析2020

    • Author(s)
      鈴木優子
    • Organizer
      第97回日本生理学会大会(誌上開催)
    • Related Report
      2019 Research-status Report
  • [Presentation] Platelet-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI)2019

    • Author(s)
      Yuko Suzuki
    • Organizer
      The XXVII Congress of the International Society on Thrombosis and Haemostasis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] thrombin-activatable fibrinolysis inhibitor活性化機構の時空間的解析2019

    • Author(s)
      鈴木優子
    • Organizer
      第41回日本血栓止血学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 活性化血小板に基づく線溶反応の時空間的解析2019

    • Author(s)
      鈴木優子
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 血漿中線溶抵抗活性の評価方法2021

    • Inventor(s)
      鈴木優子、浦野哲盟
    • Industrial Property Rights Holder
      国立大学法人浜松医科大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-177098
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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