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The effect of ADAMTS13 on the pathophysiology of sepsis

Research Project

Project/Area Number 24592744
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NISHIO KENJI  奈良県立医科大学, 医学部, 教授 (60254489)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsvon Willebrand factor / ADAMTS13 / inflammation / infarction / sepsis / 敗血症 / 炎症
Outline of Final Research Achievements

The function of von Willebrand factor (VWF) is essential for normal hemostasis and regulated by ADAMTS13 which cleaves VWF to smaller less-active forms.
We recently found that ADAMTS13 plays a role in safeguarding the myocardium from coronary artery ischemia by reducing VWF-dependent inflammation as well as thrombosis. Next we studied VWF contribution to pathophysiology of sepsis using a mouse model of experimental sepsis involving cecal ligation and puncture (CLP). VWF gene-deleted (VWF-/-; knock-out: KO) mice showed a significantly lower survival rate than wild-type mice after CLP. From those findings, in different types of inflammation, suppression of VWF function may lead to harm body. We need to study more about these differences.
The ratio of VWF-propeptide to ADAMTS13 is associated with disease severity in patients with severe sepsis or septic shock. It means that it may be possible that correcting the imbalance between VWF and ADAMTS13 could be therapeutically useful.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (4 results)

All 2014 2013 2012

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (2 results)

  • [Journal Article] Ratio of von Willebrand Factor Propeptide to ADAMTS13 Is Associated With Severity of Sepsis.2013

    • Author(s)
      Fukushima H, Nishio K, Asai H, Watanabe T, Seki T, Matsui H, Sugimoto M, Matsumoto M, Fujimura Y, Okuchi K.
    • Journal Title

      Shock.

      Volume: 39 Issue: 5 Pages: 409-414

    • DOI

      10.1097/shk.0b013e3182908ea7

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ADAMTS13 safeguards the myocardium in a mouse model of acute myocardial infarction.2012

    • Author(s)
      Masaaki Doi, Hideto Matsui, Yukiji Takeda, Yoshihiko Saito, Maiko Takeda, Yasunori Matsunari, Kenji Nishio, Midori Shima, Fumiaki Banno, Masashi Akiyama, Koichi Kokame, Toshiyuki Miyata, and Mitsuhiko Sugimoto.
    • Journal Title

      Thromb. Haemost.

      Volume: 108 Issue: 12 Pages: 1236-1238

    • DOI

      10.1160/th12-09-0674

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] von Willebrand Factor-Dependent Inflammatory Responses in Mouse Septic Model by Cecal Ligation and Puncture2014

    • Author(s)
      Shogo Kasuda, Hideto Matsui, Shiro Ono, Yasunori Matsunari, Kenji Nishio, Midori Shima, Katsuhiko Hatake and Mitsuhiko Sugimoto
    • Organizer
      2014ASH (American Society of Hematology) meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] A possible new therapeutic strategy with ADAMTS13 for cerebral infarction.2012

    • Author(s)
      Kenji Nishio
    • Organizer
      SIRIC International Symposium 2012 Perspectives in disease models of the Heart and the Brain of Mice and Men.
    • Place of Presentation
      Seoul (Korea)
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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