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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1295-1298.
Prepublished online as a Blood First Edition Paper on October 10, 2007; DOI 10.1182/blood-2007-09-110700.


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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Brief Report

Functional imaging of shear-dependent activity of ADAMTS13 in regulating mural thrombus growth under whole blood flow conditions

Yasuaki Shida1, Kenji Nishio2, Mitsuhiko Sugimoto1, Tomohiro Mizuno1, Masaaki Hamada1, Seiji Kato3, Masanori Matsumoto3, Kazuo Okuchi2, Yoshihiro Fujimura3, and Akira Yoshioka1

Departments of1 Pediatrics, 2 Emergency and Critical Care Medicine, and 3 Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan

The metalloprotease ADAMTS13 is assumed to regulate the functional levels of von Willebrand factor (VWF) appropriate for normal hemostasis in vivo by reducing VWF multimer size, which directly represents the thrombogenic activity of this factor. Using an in vitro perfusion chamber system, we studied the mechanisms of ADAMTS13 action during platelet thrombus formation on a collagen surface under whole blood flow conditions. Inhibition studies with a function-blocking anti-ADAMTS13 antibody, combined with immunostaining of thrombi with an anti-VWF monoclonal antibody that specifically reflects the VWF-cleaving activity of ADAMTS13, provided visual evidence for a shear rate–dependent action of ADAMTS13 that limits thrombus growth directly at the site of the ongoing thrombus generation process. Our results identify an exquisitely specific regulatory mechanism that prevents arterial occlusion under high shear rate conditions during mural thrombogenesis.


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