The effect of ADAMTS13 on the pathophysiology of sepsis

• Project/Area Number: 24592744
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Nara 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: ¥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)
• Keywords: von 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.

Research Products

• [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
  • 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
  • Peer Reviewed
• [Presentation] von Willebrand Factor-Dependent Inflammatory Responses in Mouse Septic Model by Cecal Ligation and Puncture (2014)
  • 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
• [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)