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Cross-talk regulation by platelets, coagulation system and fibrinolysis system in response to sepsis

Research Project

Project/Area Number 26462335
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionGifu University

Principal Investigator

akamatsu shigeru  岐阜大学, 大学院医学系研究科, 非常勤講師 (20167828)

Co-Investigator(Kenkyū-buntansha) 小澤 修  岐阜大学, 大学院医学系研究科, 教授 (90225417)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords血小板 / 凝固因子 / 線溶系 / 血栓 / PDGF-AB / 可溶型 / CD40 ligand / HSP27 / 凝固系 / コラーゲン / スフィンゴシン1リン酸 / p38 MAP kinase / 活性化第X因子 / p44/p42 MAP kinase / thromboxane A2 / Rac / soluble CD40 ligand
Outline of Final Research Achievements

Selective inhibitors of factor Xa (FXa) are widely recognized as useful therapeutic tools for stroke prevention in non-valvular atrial fibrillation or venous thrombosis. Thrombin generated by the activation of factor X to FXa, acts as a potent activator of human platelets. However, little is known whether FXa inhibitors directly affect the function of human platelets. We previously demonstrated that collagen induces the phosphorylation of heat shock protein 27 (HSP27), a small-molecular weight HSP via p44/p42 mitogen-activated protein (MAP) kinase in human platelets, eventually resulting in the release of HSP27. In the present study, we investigated the direct effect of FXa inhibitors (edoxaban and rivaroxaban) on the collagen-induced human platelet activation. Our results strongly suggest that FXa inhibitor reduces the collagen-stimulated release of phosphorylated HSP27 from human platelets due to the inhibition of HSP27 phosphorylation via p44/p42 MAP kinase.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (14 results)

All 2017 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] AICAR reduces collagen-stimulated secretion of PDGF-AB and release of soluble CD40 ligand from human platelets: suppression of HSP27 phosphorylation via p44/p42 MAP kinase.2016

    • Author(s)
      Tsujimoto M, Tokuda H, Kuroyanagi G, Yamamoto N, Kainuma S, Matsushima-Nishiwaki R, Onuma T, Iida Y, Kojima A, Sawada S, Doi T, Enomoto Y, Tanabe K, Akamatsu S, Iida H, Ogura S, Otsuka T, Kozawa O and Iwama T
    • Journal Title

      Exp Ther Med.

      Volume: 12 Pages: 1107-1112

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Thrombin Receptor-Activating Protein (TRAP)-Activated Akt Is Involved in the Release of Phosphorylated-HSP27 (HSPB1) from Platelets in DM Patients.2016

    • Author(s)
      Tokuda H, Kuroyanagi G, Tsujimoto M, Matsushima-Nishiwaki R, Akamatsu S, Enomoto Y, Iida H, Otsuka T, Ogura S, Iwama T, Kojima K, Kozawa O.
    • Journal Title

      Int J Mol Sci

      Volume: 17 Issue: 5 Pages: 737-737

    • DOI

      10.3390/ijms17050737

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Factor Xa inhibitor suppresses the release of phosphorylated HSP27 from collagen-stimulated human platelets: inhibition of HSP27 phosphorylation via p44/p42 MAP kinase.2016

    • Author(s)
      Tsujimoto M, Kuroyanagi G, Matsushima-Nishiwaki R, Kito Y, Enomoto Y, Iida H, Ogura S, Otsuka T, Tokuda H, Kozawa O and Iwama T.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 4 Pages: e0151907-e0151907

    • DOI

      10.1371/journal.pone.0151907

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of Rac in thromboxane A2-induced human platelet activation: Regulation of sCD40 ligand release and PDGF-AB secretion.2014

    • Author(s)
      Kageyama Y, Doi T, Matsushima-Nishiwaki R, Iida Y, Akamatsu S, Kondo A, Kuroyanagi G, Yamamoto N, Mizutani J, Otsuka T, Tokuda H, Iida H, Kozawa O, Ogura S.
    • Journal Title

      Mol Med Rep.

      Volume: 10(1) Issue: 1 Pages: 107-12

    • DOI

      10.3892/mmr.2014.2143

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 早期からのエポプロステノール併用Upfront Combination Therapyが有効であった重症肺高血圧症の一例2017

    • Author(s)
      森下健太郎,勝木竜介,三鴨 肇,森 茂,道野朋洋,赤松 繁,香田雅彦,鷹津久登
    • Organizer
      第44回日本集中治療医学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2016 Annual Research Report
  • [Presentation] The role of Rac in human platelets: An analysis of the molecular mechanism underlying Rac-effects on the activation2016

    • Author(s)
      Doi Tomoaki、Kozawa Osamu、Kageyama Yasunari、Ogura Shinji
    • Organizer
      Thirty-eight Annual Conference on Shock
    • Place of Presentation
      Denver, USA
    • Year and Date
      2016-06-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血小板の炎症誘導作用におけるRacの役割2016

    • Author(s)
      土井智章、陰山康成、小澤 修、小倉真治
    • Organizer
      第31回日本Shock学会総会
    • Place of Presentation
      東京
    • Related Report
      2016 Annual Research Report
  • [Presentation] Sphigosine-1-phosphate suppresses collagen-induced human platelet activation.2016

    • Author(s)
      Onuma T, Tanabe K, Kozawa O, Iida H.
    • Organizer
      Anesthesiology 2016 Annual Meeting
    • Place of Presentation
      Chicago
    • Related Report
      2016 Annual Research Report
  • [Presentation] Tracheal Bronchusのためダブルルーメンチューブの適切位置への留置に難渋した肺腫瘍症例.2016

    • Author(s)
      杉本純子,道野朋洋,赤松繁
    • Organizer
      日本麻酔科学会東海北陸支部第14回学術集会
    • Place of Presentation
      津
    • Related Report
      2016 Annual Research Report
  • [Presentation] 20種類以上の多剤を内服していた長期透析患者の麻酔経験2016

    • Author(s)
      山本恭介,道野朋洋,杉本純子,河村三千香,赤松繁
    • Organizer
      日本麻酔科学会東海北陸支部第14回学術集会
    • Place of Presentation
      津
    • Related Report
      2016 Annual Research Report
  • [Presentation] 心機能をTEEでどう捉えるか.TEEセミナー「心機能とTEE」2016

    • Author(s)
      赤松 繁
    • Organizer
      日本心臓血管麻酔学会第21回学術大会
    • Place of Presentation
      横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] 急激な経過で破裂したサルモネラ菌による感染性腹部大動脈瘤の一例2015

    • Author(s)
      関谷憲晃,湯本和也,三鴨 肇,森 茂,赤松 繁,景山聡一郎
    • Organizer
      第18回日本救急医学会中部地方会
    • Place of Presentation
      福井市
    • Year and Date
      2015-12-12
    • Related Report
      2015 Research-status Report
  • [Presentation] 非心臓手術におけるTEEの役割2015

    • Author(s)
      赤松 繁
    • Organizer
      第20回日本心臓血管麻酔学会
    • Place of Presentation
      福岡市
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 血小板機能におけるRacの役割:抗炎症作用の分子機序解析2014

    • Author(s)
      土井智章、陰山康成、小澤 修、小倉真治
    • Organizer
      第29回日本Shock学会
    • Place of Presentation
      松山
    • Year and Date
      2014-05-17
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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