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Involvement of ADAMTS-13 in the pathogenesis of acute coronary syndrome

Research Project

Project/Area Number 18590336
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionUniversity of Miyazaki

Principal Investigator

HATAKEYAMA Kinta  University of Miyazaki, Dept of Pathology, Assistant prof. (60325735)

Co-Investigator(Kenkyū-buntansha) MARUTSUKA Kousuke  University of Miyazaki, Dept of Pathology, Associate prof. (00239154)
SATO Yuichirou  University of Miyazaki, Dept of Pathology, Assistant prof. (90347055)
IMAMURA Takuroh  University of Miyazaki, Dept of Medicine, Assistant prof. (60203329)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsImmunohistochemistry / ADAMTS-13 / Atherothroinhosis / Von Willebrand factor / Acute myocardial infarction / Histopathology / Flow chamber / rabbit femoral artery / 冠動脈アテレクトミー / 動脈硬化 / 血栓 / 炎症
Research Abstract

Background : Disruption of atherosclerotic plaque with subsequent thrombus formation is a major cause of atherothrombosis. Von Willebrand factor (VWF), ultra-large multimers of which are cleaved by ADAMTS-13, plays a important role in thrombus formation. However, the role of ADAMTS-13 during thrombogenesis remains unknown. Methods and Results : We studied the localization of ADAMTS-13 in fresh coronary thrombi obtained from patients with acute myocardial infarction (AMI). We also examined the roles of ADAMTS-13 in thrombus formation using collagen-coated flow chambers (100S-1 and 1,500S-1) and on injured neointima of rabbit femoral arteries. ADAMTS-13 was detected in thrombi of AMI and in the flow chamber, where it colocalized with VWF. The surface area covered by platelet adhesion and the long axes of platelet thrombi were higher under 1,500S^-1 than under 100S^-1 of shear rate, and both the area and long axes were significantly augmented with an antibody to the ADAMTS-13 disintegrin-like domain (WH2-22-1A), but not to the thrombospondin 1-3 domain (WH10) under 1,500S^-1 of shear rate. WH2-22-1A, but not WH10, reduced the activity of plasma ADAMTS-13 to cleave large VWF multimers during perfusion. Reducing ADAMTS-13 activity with WH2-22-1A also resulted in the significant augmentation of thrombus formation on injured neointima of rabbit femoral arteries in vivo. Conclusion : These clinical, in vitro human blood, and in vivo animal experiments suggest the role of disintegrin-like domain of ADAMTS-13 in down-regulating the thrombus growth on diseased arteries under high shear rate conditions.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (11 results)

All 2007 2006

All Journal Article (9 results) (of which Peer Reviewed: 3 results) Presentation (1 results) Book (1 results)

  • [Journal Article] Tissue factor pathway inhibitor is highly susceptible to chymase-mediated proteolysis2007

    • Author(s)
      Hamuro T, et. al.
    • Journal Title

      FEBS J 274

      Pages: 3065-3077

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome2007

    • Author(s)
      Myoishi M, et. al.
    • Journal Title

      Circulation 116

      Pages: 1226-1233

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression of interleukin-18 in coronary plaque obtained by atherectomy from patients with stable and unstable angina2007

    • Author(s)
      Nishihira K, et. al.
    • Journal Title

      Thromb Res 121

      Pages: 275-279

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Tissue factor pathway inhibitor is highly susceptible to chymase-mediated proteolysis2007

    • Author(s)
      Hamuro, T, et. al.
    • Journal Title

      FEBS J 274

      Pages: 3065-77

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome2007

    • Author(s)
      Myoishi, M, et. al.
    • Journal Title

      Circulation 116

      Pages: 1226-33

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of interleukin-18 in coronary plaque obtained by atherectomy from patients with stable and unstable angina2007

    • Author(s)
      Nishihira, K, et. al.
    • Journal Title

      Thromb Res 121

      Pages: 275-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] アテローム血栓症における炎症性因子の関与2007

    • Author(s)
      畠山金太, 浅田祐士郎
    • Journal Title

      内分泌・糖尿病科 24

      Pages: 298-303

    • NAID

      120007123090

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 冠動脈血栓の成り立ち2006

    • Author(s)
      畠山金太, 浅田祐士郎
    • Journal Title

      Coronary Intervention 2

      Pages: 10-16

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 病理学的立場から内皮機能改善と心筋梗塞発症予防を探る2006

    • Author(s)
      畠山金太, 浅田祐士郎
    • Journal Title

      Vascular Medicine 2

      Pages: 240-246

    • Related Report
      2006 Annual Research Report
  • [Presentation] Relation of PTX3 to plaque instability and restenosis in directional atherectomy specimens from patients with stable angina and acute coronary syndromes2007

    • Author(s)
      Hatakeyama K, et. al.
    • Organizer
      76th annual EAS Congress
    • Place of Presentation
      Helsinki
    • Year and Date
      2007-06-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 血栓症ナビゲーター2006

    • Author(s)
      池田康夫監修, (畠山金太, 浅田祐士郎分担)
    • Total Pages
      317
    • Publisher
      メディカルレビュー社
    • Related Report
      2006 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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