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The true significance of platelet activation in hypothermia - physiological functional analysis and biological effects.

Research Project

Project/Area Number 21K17328
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 58040:Forensics medicine-related
Research InstitutionInternational University of Health and Welfare

Principal Investigator

HORIOKA KIE  国際医療福祉大学, 医学部, 助教 (20897730)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords低体温症 / 血小板 / 脾臓 / PDMV / 低体温
Outline of Research at the Start

低体温症は深部体温が低下することにより様々な障害を引き起こす病態であり、重症例は治療が難しく非常に致死率が高いが、低体温症の詳細な病態については未だ明らかになっていない。これまでの解析から、低体温症の脾臓内で血小板が活性化することを明らかにしてきた。血小板の活性化は血栓性の病態を引き起こす一方、組織再生といった生体防御に有益な作用をもたらすことから、低体温症における生命維持のための生体防御反応として重要な意義をもつ可能性がある。本研究では、活性化血小板とそれから放出される分子の役割を解明し、低体温症の治療・予防に繋げる。

Outline of Final Research Achievements

This study aimed to clarify the function of activated platelets in hypothermia by analysing platelet-derived microvesicles (PDMVs) released by activated platelets during hypothermia and the molecules encapsulated in them, with the following results. (1) A comprehensive genetic analysis of platelets in the spleen and peripheral blood revealed that platelets activated by hypothermia release factors involved in tissue repair. (2) PDMV was demonstrated to be released from platelets in the spleen during hypothermia. (3) PDMV released from hypothermic intrasplenic platelets contained tissue repair factors.

Academic Significance and Societal Importance of the Research Achievements

本研究成果から、低体温時の脾臓内血小板活性化がPDMVsを放出すること、さらにPDMVsに組織修復因子を内包するという新たな知見を得ることができた。今後、低体温症時に生じる生体へのダメージや活性化血小板やPDMVsの作用対象臓器を解析することによって、活性化血小板やPDMVsが生体に与える組織修復作用機序を解明できる可能性がある。これらの成果は、救急医学における低体温症治療の一助になることが期待される。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (16 results)

All 2023 2022 2021 Other

All Int'l Joint Research (3 results) Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (8 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] University of Oulu/Department of Forensic Medicine(フィンランド)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Karolinska Institutet/Department of Oncology-Pathology(スウェーデン)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Karolinska Institutet(スウェーデン)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Bioprotective role of platelet-derived microvesicles in hypothermia: Insight into the differential characteristics of peripheral and splenic platelets2023

    • Author(s)
      Horioka Kie、Tanaka Hiroki、Okaba Keisuke、Yamada Shinnosuke、Hayakawa Akira、Ishii Namiko、Motomura Ayumi、Inoue Hiroyuki、Takauji Shuhei、Isozaki Shotaro、Ogawa Katsuhiro、Yajima Daisuke、Druid Henrik、Pakanen Lasse、Porvari Katja
    • Journal Title

      Thrombosis Research

      Volume: 223 Pages: 155-167

    • DOI

      10.1016/j.thromres.2023.01.006

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypoxia-induced nuclear translocation of β-catenin in the healing process of frostbite2022

    • Author(s)
      Isozaki Shotaro、Tanaka Hiroki、Horioka Kie、Konishi Hiroaki、Kashima Shin、Takauji Shuhei、Fujiya Mikihiro、Druid Henrik
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

      Volume: 1868 Issue: 6 Pages: 166385-166385

    • DOI

      10.1016/j.bbadis.2022.166385

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Soluble thrombomodulin ameliorates aberrant hemostasis after rewarming in a rat accidental hypothermia model2022

    • Author(s)
      Takauji Shuhei、Tanaka Hiroki、Hayakawa Mineji、Horioka Kie、Isozaki Shotaro、Konishi Hiroaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 587 Pages: 1-8

    • DOI

      10.1016/j.bbrc.2021.11.086

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Treatment of hepatocellular carcinoma with autologous platelets encapsulating sorafenib or lenvatinib: A novel therapy exploiting tumor‐platelet interactions2021

    • Author(s)
      Tanaka Hiroki、Horioka Kie、Hasebe Takumu、Sawada Koji、Nakajima Shunsuke、Konishi Hiroaki、Isozaki Shotaro、Goto Masanori、Fujii Yumiko、Kamikokura Yuki、Ogawa Katsuhiro、Nishikawa Yuji
    • Journal Title

      International Journal of Cancer

      Volume: 150 Issue: 10 Pages: 1640-1653

    • DOI

      10.1002/ijc.33915

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypothermia causes platelet activation in the human spleen2021

    • Author(s)
      Horioka Kie、Tanaka Hiroki、Okaba Keisuke、Yamada Shinnosuke、Ishii Namiko、Motomura Ayumi、Inoue Hiroyuki、Alkass Kanar、Druid Henrik、Yajima Daisuke
    • Journal Title

      Thrombosis Research

      Volume: 205 Pages: 47-55

    • DOI

      10.1016/j.thromres.2021.06.023

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] BioprotectiveRoleofPlatelet-DerivedMicrovesiclesinHypothermia:InsightsfromtheDifferential Characteristics of Peripheral and Splenic Platelets2022

    • Author(s)
      Kie Horioka
    • Organizer
      American Society of Hematology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Rewarming from accidental hypothermia enhances whole blood coagulation in a mouse model2022

    • Author(s)
      Kie Horioka
    • Organizer
      International society on Thrombosis and Haemostasis
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Rewarming from accidental hypothermia enhances whole blood clotting properties in a murine model2022

    • Author(s)
      Kie Horioka
    • Organizer
      The 21th Nordic Conference on Forensic Medicine
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 自己血小板を用いたドラッグデリバリーシステムの肝細胞癌に対するターゲティング効果2021

    • Author(s)
      田中 宏樹, 堀岡 希衣, 後藤 正憲, 人見 淳一, 藤井 裕美子, 上小倉 佑機, 孟 玲童, 小川 勝洋, 西川 祐司
    • Organizer
      日本癌学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 低体温症における血小板変化と血液凝固機能異常2021

    • Author(s)
      堀岡 希衣, 田中 宏樹, 岡馬 恵介, 石井 名実子, 本村 あゆみ, 井上 博之, 矢島 大介
    • Organizer
      日本血栓止血学
    • Related Report
      2021 Research-status Report
  • [Presentation] 自己血小板を利用したドラッグデリバリーシステム 肝癌・血小板相互作用を利用した新たな治療戦略2021

    • Author(s)
      田中 宏樹, 堀岡 希衣, 後藤 正憲, 人見 淳一, 藤井 裕美子, 上小倉 佑機, 孟 玲童, 小川 勝洋, 西川 祐司
    • Organizer
      日本病理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 低体温症に対する復温療法時の活性化血小板動態と血栓形成2021

    • Author(s)
      堀岡 希衣, 田中 宏樹, 岡馬 恵介, 石井 名実子, 本村 あゆみ, 井上 博之, 矢島 大介
    • Organizer
      日本病理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Activation of intra-splenic platelets as a pathologic feature during deep hypothermia.2021

    • Author(s)
      Horioka K, Tanaka H, Isozaki S, Henrik D
    • Organizer
      International society on Thrombosis and Haemostasis
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2024-01-30  

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