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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1105.)
© 2003 American Heart Association, Inc.

Thrombosis

Contribution of von Willebrand Factor to Thrombus Formation on Neointima of Rabbit Stenotic Iliac Artery Under High Blood-Flow Velocity

Atsushi Yamashita; Yujiro Asada; Hiroshi Sugimura; Hiroshi Yamamoto; Kousuke Marutsuka; Kinta Hatakeyama; Shozo Tamura; Yasuo Ikeda; Akinobu Sumiyoshi

From the First Department of Pathology (A.Y., Y.A., K.M., K.H., A.S.) and the Department of Radiology (H.S., S.T.), Miyazaki Medical College, Miyazaki; Pharmaceutical Research Laboratories (H.Y.), Ajinomoto Co, Inc, Kawasaki; and the Department of Medicine (Hematology) (Y.I.), Keio University School of Medicine, Tokyo, Japan.

Correspondence to Yujiro Asada, MD, First Department of Pathology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. E-mail yasada{at}fc.miyazaki-med.ac.jp

Objective— It has become clear that von Willebrand factor (vWF) plays important roles in platelet adhesion and aggregation under high blood-flow velocity conditions observed in stenotic atherosclerotic arteries. However, its roles in thrombus formation in vivo on diseased arteries have not been fully understood. We examined the contribution of vWF to thrombus formation and subsequent intimal growth by using a repeated balloon-injury model in rabbits.

Methods and Results— Rabbit iliac arteries 4 weeks after a first balloon injury showed 37% luminal stenosis by neointimal growth, and blood velocity increased by 2.1 times compared with that of uninjured arteries. The second balloon injury induced fibrin-rich thrombus formation on the injured neointima. Intravenous administration of a monoclonal antibody against vWF (AJW200, 1.0 mg/kg body weight) remarkably prevented botrocetin-induced platelet aggregation ex vivo for 2 days; moreover, thrombus formation, cell proliferation, and subsequent neointimal growth were significantly reduced at 30 minutes, 5 days, and 4 weeks, respectively, after the second balloon injury.

Conclusions— These results indicate that vWF plays a potent role in fibrin-rich thrombus formation on the neointima under high blood-flow velocity conditions. Inhibition of plasma vWF activity might be effective for the reduction of thrombus formation and/or subsequent neointimal development after coronary interventions.

Key Words: von Willebrand factor • thrombosis • blood flow • rabbits • AJW200

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