2007 Fiscal Year Final Research Report Summary
Involvement of ADAMTS-13 in the pathogenesis of acute coronary syndrome
| Project/Area Number |
18590336
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
HATAKEYAMA Kinta University of Miyazaki, Dept of Pathology, Assistant prof. (60325735)
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| 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)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Immunohistochemistry / ADAMTS-13 / Atherothroinhosis / Von Willebrand factor / Acute myocardial infarction / Histopathology / Flow chamber / rabbit femoral artery |
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| 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.
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Research Products
(7 results)
