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Elucidation of the dynamics and pathophysiological role of microparticles in septic DIC

Research Project

Project/Area Number 21K09064
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55060:Emergency medicine-related
Research InstitutionTohoku University

Principal Investigator

Saito Koji  東北大学, 医学系研究科, 非常勤講師 (10359515)

Co-Investigator(Kenkyū-buntansha) 山田 充啓  東北大学, 大学病院, 講師 (00396483)
武井 祐介  東北大学, 大学病院, 助教 (80822890)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords細胞外小胞 / マイクロパーティクル / 敗血症 / 播種性血管内凝固症候群 / COVID-19 / DIC / microparticles
Outline of Research at the Start

敗血症性DICの真の病態を反映するマーカーや治療法は確立されていない。マイクロパーティクル(MPs: microparticles)に着目し,敗血症性DICのMPsの動態の解明, 病態マーカーの確立, そして敗血症性DICにおけるMPsの病態生理学的作用を検証する。本課題では,1)敗血症性DIC患者のMPsの動態,2)敗血症性DIC患者由来MPsのトロンビン生成に対する影響,3)MPsに含まれるmRNAおよびmiRNAの網羅的解析,4)MPsの培養内皮細胞,単球,好中球に対する影響を検証する。MPsの動態とその病態生理学的作用を解明することで,敗血症性DICの新たな病態マーカーの開発を目指す。

Outline of Final Research Achievements

To establish a diagnostic and evaluation marker for COVID-19-related coagulation disorders, we conducted an multi-center prospective study and measured microparticles in the plasma of COVID-19 patients. CD41+MPs were elevated in the coagulopathy (D-dimer ≧ 1 μg/mL) group compared to healthy volunteers, and CD41+MPs was weakly correlated with thrombin generation capacity.
Evaluation of circulating microparticles in septic patients showed that CD62P+MPs and CD14+MPs were significantly elevated in patients with septic DIC compared that without DIC, suggesting the involvement of platelet activation and monocytes in the development of septic DIC.

Academic Significance and Societal Importance of the Research Achievements

COVID-19関連凝固障害や敗血症性播種性血管内凝固症候群(DIC)は、様々な因子が関与する複雑な病態を呈するが、病態を反映するマーカーが確立されていない。本課題では、COVID-19関連凝固障害では血小板由来のCD41+microparticles(MPs)が、敗血症性DICでは活性化血小板由来のCD62P+MPsと探求由来のCD14+MPsが上昇していることを報告した。細胞外小胞がこれらのあらたな病態マーカーとなりえることが示唆された。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (2 results)

All 2023

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

  • [Journal Article] Circulating Extracellular Vesicle Levels in Patients with Coronavirus Disease 2019 Coagulopathy: A Prospective Cohort Study2023

    • Author(s)
      Yudai Iwasaki, Yusuke Takei, Mitsuhiro Yamada, Shigekazu Sugino, Koji Saito, Tetsuji Aoyagi, Kengo Oshima, Hajime Kanamori, Hiroaki Baba, Kentarou Takei, Koichi Tokuda, Eichi N. Kodama, Tetsuro Kamo, Tadashi Kamio, Takehiko Kasai, Satoru Ogawa, Masanori Yamauchi.
    • Journal Title

      Journal of Clinical Medicine

      Volume: 12 Issue: 10 Pages: 3460-3460

    • DOI

      10.3390/jcm12103460

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 細胞外小胞に着目した人工呼吸関連肺傷害の内皮傷害マーカーの探索2023

    • Author(s)
      武井 祐介、岩崎 夢大、紺野 大輔、入間田 大介、関根 智宏、齋藤 秀悠、杉野 繁一、山内 正憲
    • Organizer
      第50回 日本集中治療医学会 学術集会
    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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