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Role of factor XI on pulmonary thromboembolism: development for novel anticoagulant

Research Project

Project/Area Number 19K07437
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionUniversity of Miyazaki

Principal Investigator

Yamashita Atsushi  宮崎大学, 医学部, 准教授 (90372797)

Co-Investigator(Kenkyū-buntansha) 古小路 英二  宮崎大学, 医学部, 講師 (00423723)
田島 卓也  宮崎大学, 医学部, 講師 (80549056)
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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsfactor XI / venous thromboembolism / pathology / Factor XI / 肺血栓塞栓症 / 深部静脈血栓血栓症 / 血液凝固XI因子
Outline of Research at the Start

肺血栓塞栓症は、下肢や骨盤内の静脈にできた血栓が遊離し、肺動脈をつまらせることで発症する疾患です。しかし、静脈血栓がどのように形成されるのかは明確ではなく、現在の予防薬は出血性副作用が生じることがあり、安全な薬剤の開発が重要です。申請者らは血液凝固XI因子 (FXI) の欠損症では出血傾向が少ないこと注目し研究を進めてきました。しかし肺血栓塞栓症の発症におけるFXIの役割は完全には明らかとなっていません。
本研究では、①静脈血栓にFXIが存在するかどうかを明らかにすること、②静脈血栓の大きさに影響する因子とFXIの関与を明らかにすることを目的とします。

Outline of Final Research Achievements

Current oral anticoagulant is widely used for prevention and treatment of pulmonary thromboembolism. However, bleeding complications remain a critical problem. We found that factor XI is predominantly localized in non-organizing area of deep vein thrombus, and that factor XI play a minor role in fibrin formation in a flow chamber system, compared with factor X.

Academic Significance and Societal Importance of the Research Achievements

肺血栓塞栓症の予防・治療に血液の凝固を抑える経口抗凝固薬が使用されています。一定の効果を得られていますが、血液凝固反応を抑えるため出血性副作用が問題となっています。本研究では止血作用への関与が少ないとされる血液凝固XI因子に注目しました。血液凝固XI因子が静脈血栓に存在し、抗血栓作用が現在の薬剤よりも強力ではないこと明らかにした本研究成果は、血液凝固XI因子を標的とした新規抗凝固薬の開発において重要な情報を提供すると考えられます。

Report

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

    (5 results)

All 2021 2020

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] MRI diffusion-weighted imaging detects a fresh portal vein thrombus as a high intensity lesion in a patient with a liver transplant: A case report2021

    • Author(s)
      Kuroiwa Yasuyoshi、Kusumoto Kazunori、Shimata Keita、Yamashita Atsushi、Hibi Taizo、Asada Yujiro、Imamura Takuroh
    • Journal Title

      Acta Radiologica Open

      Volume: 10 Issue: 12 Pages: 1-4

    • DOI

      10.1177/20584601211069557

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathological features of ruptured coronary plaque and thrombus interfaces: fibrin and von Willebrand factor as platelet scaffolds on rupture sites2021

    • Author(s)
      Yamashita A, Nishihira K, Gi T, Maekawa K, Hatakeyama K, Horiuchi S, Wada K, Shibata Y, Asada Y.
    • Journal Title

      Thromb Haemost.

      Volume: 121 Issue: 02 Pages: 234-241

    • DOI

      10.1055/s-0040-1716539

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tissue factor expression and tumor-infiltrating T lymphocytes in ovarian carcinomas and their association with venous thromboembolism2020

    • Author(s)
      Gi T, Yamashita A, Aman M, Kuwahara A, Asada Y, Kawagoe Y, Onishi J, Sameshima H, Sato Y.
    • Journal Title

      Pathology International

      Volume: 71 Issue: 4 Pages: 261-266

    • DOI

      10.1111/pin.13074

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Signal change of jugular vein thrombus on diffusion-weighted magnetic resonance imaging.2020

    • Author(s)
      Kuga N, Kuroiwa Y, Sakamoto T, Yamashita A, Gi T, Doi Shogo, Kinoshita T, Tanaka T, Kihara Y, Asada Y, Imamura T.
    • Journal Title

      Circ Rep.

      Volume: 2 Issue: 8 Pages: 455-456

    • DOI

      10.1253/circrep.cr-20-0039

    • NAID

      130007885741

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 家兎静脈血栓モデルによる経口活性化凝固XIa因子阻害薬(ONO-1600586)の抗血栓作用と止血への影響2021

    • Author(s)
      大栗伸行, 山下 篤, 神山 祥, 大川星美, 浅田祐士郎
    • Organizer
      第43回日本血栓止血学会
    • Related Report
      2021 Annual Research Report

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

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