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The response of endothelial cells and the function of coagulation factor VIII under flow conditions

Research Project

Project/Area Number 17K10126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionNara Medical University

Principal Investigator

Shida Yasuaki  奈良県立医科大学, 医学部, 研究員 (10721566)

Co-Investigator(Kenkyū-buntansha) 野上 恵嗣  奈良県立医科大学, 医学部, 准教授 (50326328)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords血液 / 血流 / 血栓止血 / 凝固因子 / FVIII / 血管内皮 / shear stress / 血管内皮細胞 / 第VIII因子 / von Willebrand 因子 / 生理学 / 蛋白質 / 内科
Outline of Final Research Achievements

Coagulation factor VIII (FVIII) and von Willebrand factor (VWF) are essential factors for hemostasis. Although these proteins are produced in endothelial cells, the detailed mechanism is not known. We evaluated the influence of shear stress created by the blood flow on the production of FVIII and VWF. Shear stress not only changed the shape of endothelial cells but also accelerated the production of FVIII and VWF. Furthermore, the pattern of blood flow such as laminar and oscillatory flow had distinct effects on the production. These results identified the novel regulatory mechanism of hemostasis and, moreover, are applicable to improved efficiency of the production of FVIII and VWF.

Academic Significance and Societal Importance of the Research Achievements

止血に必須の凝固因子である第 VIII因子(FVIII)や血小板粘着凝集に関わるフォン・ヴィレブランド因子(VWF)は血管内皮細胞で産生されることが知られているが、その詳細な機序は不明である。今回我々は血流がこれらの因子産生に及ぼす影響を独自の還流装置を用いて検討した。血流により血管内皮細胞は形態変化を起こすだけでなく、VWFやFVIIIの産生を亢進させた。また層流や乱流などの血流形式によっても異なることが判明した。新たな止血制御機構の解明であり、またFVIIIやVWF因子製剤の効率良い製造にも応用できる可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Shear stress and platelet-induced tensile forces regulate ADAMTS13-localization within the platelet thrombus.2019

    • Author(s)
      Shida Y, Swystun LL, Brown C, Mewburn J, Nesbitt K, Danisment O, Riches JJ, Hough C, Lillicrap D.
    • Journal Title

      Res Pract Thromb Haemost.

      Volume: 2 Issue: 2 Pages: 254-260

    • DOI

      10.1002/rth2.12196

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Global coagulation function assessed by rotational thromboelastometrypredicts coagulation-steady state in individual hemophilia A patients receiving emicizumab prophylaxis.2019

    • Author(s)
      Yada K , Nogami K, Ogiwara K, Shida Y, Furukawa S, Yaoi H, Takeyama M, Kasai R,Shima M.
    • Journal Title

      International Journal of Haematology

      Volume: 110(4) Issue: 4 Pages: 419-430

    • DOI

      10.1007/s12185-019-02698-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of moderate haemophilia A with inhibitor, carrying the p.R1800H mutation, complicated with juvenile idiopathic arthritis2018

    • Author(s)
      Yuka Kondo Yasuaki Shida Tomoaki Ishikawa Koji Yada Masahiro Takeyama Midori Shima Keiji Nogami
    • Journal Title

      Haemophilia

      Volume: 25(1) Issue: 1 Pages: 51-54

    • DOI

      10.1111/hae.13648

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Factor (F)VIII/VIIa enhances global haemostatic function in the co-presence of bypassing agents and FVIII among patients with haemophilia A with inhibitor2018

    • Author(s)
      Nogami K, Matsumoto T, Yada K, Ogiwara K, Furukawa S, Shida Y, Takeyama M, Shima M
    • Journal Title

      Br J Haematol

      Volume: ahead of printing Issue: 4 Pages: 528-536

    • DOI

      10.1111/bjh.15209

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Highly elevated plasma level of von Willebrand factor accelerates the formation of platelet thrombus under high shear stress in plasma with deficient ADAMTS13 activity.2017

    • Author(s)
      Yagi H, Yamaguchi N, Shida Y, Sugimoto M, Tubaki K, Fujimura Y, Matsumoto M
    • Journal Title

      Thromb Res

      Volume: 159 Pages: 91-95

    • DOI

      10.1016/j.thromres.2017.10.007

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of red blood cells in the anemia-associated bleeding under high shear conditions2017

    • Author(s)
      H. Yaoi, Y. Shida,, K. Ogiwara, K. Hosokawa, M. Shima and K. Nogami
    • Journal Title

      hemophilia

      Volume: - Issue: 5 Pages: 750-758

    • DOI

      10.1111/hae.13252

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Impaired thrombus formation of von Willebrand Disease under high shear flow condition is improved by factor FVIIIa mimetic bispecific antibody(emicizumab)2018

    • Author(s)
      Hiroaki Yaoi, Yasuaki Shida, Keiji Nogami, Takehisa Kitazawa, Midori Shima
    • Organizer
      world federation of hemophilia
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] VWD 各病型におけるEmicizumab の高ずり応力下での止血効果2018

    • Author(s)
      矢追博章,志田泰明,野上恵嗣,北沢剛久,嶋緑倫
    • Organizer
      第40回 日本血栓止血学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 抗FIXa/FX-bispecific抗体(Emicizumab)のType2N von Willebrand病での血流下血栓形成能の改善効果2017

    • Author(s)
      矢追博章、志田泰明、野上恵嗣、北沢剛久、服部有宏、嶋 緑倫
    • Organizer
      第39回日本血栓止血学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] FVIIIa Mimicking Bispecific Antibody (emicizumab) Improved Thrombus Formation of Type 2N von Willebrand Disease under Both High and Low Shear Conditions2017

    • Author(s)
      Hiroaki Yaoi, Yasuaki Shida, Takehisa Kitazawa、Kunihiro Hattori, Midori Shima, Keiji Nogami
    • Organizer
      International society of thrombosis and haemostasis
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Activated FVIII Released From FVIII/VWF Complex Facilitates Thrombus Development Under Flow Condition2017

    • Author(s)
      Hiroaki Yaoi, Yasuaki Shida, Takehisa Kitazawa、Kunihiro Hattori, Midori Shima, Keiji Nogami
    • Organizer
      East Asia hemophilia forum
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Factor VIIIa mimetic bispecific antibody (emicizumab) improves thrombus formation of von Willebrand disease under high shear flow condition2017

    • Author(s)
      Yasuaki Shida, Hiroaki Yaoi, Takehisa Kitazawa、Kunihiro Hattori, Midori Shima, Keiji Nogami
    • Organizer
      East Asia hemophilia forum
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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