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.

journal_name

Blood

journal_title

Blood

authors

Shida Y,Nishio K,Sugimoto M,Mizuno T,Hamada M,Kato S,Matsumoto M,Okuchi K,Fujimura Y,Yoshioka A

doi

10.1182/blood-2007-09-110700

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

1295-8

issue

3

eissn

0006-4971

issn

1528-0020

pii

blood-2007-09-110700

journal_volume

111

pub_type

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