ADAMTS-13 attenuates thrombus formation on type I collagen surface and disrupted plaques under flow conditions.
Plaque disruption with subsequent thrombus formation is a major cause of atherothrombotic diseases and von Willebrand factor (VWF), which is cleaved by ADAMTS-13, plays a critical role in thrombus formation. However, the role of ADAMTS-13 during thrombogenesis on atherosclerotic vessel remains unknown. We examined the localization of ADAMTS-13 in coronary thrombi obtained from patients with acute myocardial infarction. We also investigated the roles of ADAMTS-13 in thrombus formation using type I collagen-coated flow chambers (100S(-1) and 1500S(-1)) and on injured neointima of rabbit femoral arteries. ADAMTS-13 was present in thrombi of human coronary arteries, where it co-localized with VWF. In a flow chamber, both the average of the surface covered by platelet adhesion and the long axes of platelet thrombi were significantly augmented by an antibody to the ADAMTS-13 disintegrin-like domain (WH2-22-1A) at a shear rate of 1500s(-1), but not by an antibody to the ADAMTS-13 thrombospondin 1-3 domain (WH10). WH2-22-1A also reduced the activity of plasma ADAMTS-13 to cleave large VWF multimers during perfusion. Thrombi on injured neointima were induced by repeated balloon injury of rabbit femoral arteries, and were composed of platelet and fibrin, like human coronary thrombi. WH2-22-1A significantly augmented thrombus formation on injured neointima. These results suggest that the disintegrin-like domain of ADAMTS-13 functions in attenuating thrombus growth on diseased arteries exposed to a high shear rate.
Moriguchi-Goto
Sayaka
S
Department of Pathology, University of Miyazaki, Kiyotake, Japan.
Yamashita
Atsushi
A
Tamura
Noriko
N
Soejima
Kenji
K
Takahashi
Misaki
M
Nakagaki
Tomohiro
T
Goto
Shinya
S
Asada
Yujiro
Y
D051722:ADAM Proteins / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D050197:Atherosclerosis / Q000473:pathology*; D024042:Collagen Type I / Q000378:metabolism*; D003331:Coronary Vessels / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010973:Platelet Adhesiveness; D011817:Rabbits; D013927:Thrombosis / Q000473:pathology*; D019699:Thrombospondins / Q000737:chemistry; D014841:von Willebrand Factor / Q000378:metabolism
D024042:Collagen Type I; D019699:Thrombospondins; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human