title: Functional imaging of shear-dependent activity of ADAMTS13 in regulating mural thrombus growth under whole blood flow conditions.
abstract: 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.
authors.affiliation: Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shida
authors.forename: Kenji
authors.initials: K
authors.lastname: Nishio
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mizuno
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hamada
authors.forename: Seiji
authors.initials: S
authors.lastname: Kato
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Okuchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshioka
mesh_terms: D051722:ADAM Proteins / Q000276:immunology / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000911:Antibodies, Monoclonal / Q000276:immunology; D006801:Humans; D013927:Thrombosis / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human