Anti-human von willebrand factor monoclonal antibody AJvW-2 prevents thrombus deposition and neointima formation after balloon injury in guinea pigs.
Immediately after angioplasty, platelet adhesion to the injured arterial wall and subsequent release of various mitogens may contribute to neointima formation. The purpose of this study was to evaluate the inhibitory effect of AJvW-2, a monoclonal antibody against human von Willebrand factor (vWF), on neointima formation in a guinea pig model. The carotid artery was injured with a balloon catheter, and AJvW-2 was administered by a single bolus injection. AJvW-2 dose-dependently prevented neointima formation 14 days after injury. Significant inhibition was observed at 1.8 mg/kg, at which dose significant inhibition of platelet aggregation was achieved for 2 days. By elastic-Masson staining, organized thrombi were observed in the neointimal lesion on day 14. The thrombus area was significantly correlated with neointimal thickness. Furthermore, thrombus deposition, immunostained for vWF and fibrin(ogen), was observed on the media immediately after balloon injury. AJvW-2 significantly reduced the deposition of both adhesive proteins and reduced the incidence of organized thrombus formation, which might affect subsequent neointima formation. However, the proliferation of cultured smooth muscle cells was not affected by AJvW-2. These results suggest that AJvW-2 prevents neointima formation by inhibition of initial platelet-mediated thrombus formation rather than by direct inhibition of smooth muscle cell proliferation.
Kageyama
S
S
Developmental Research Laboratories, Pharmaceutical Research Laboratories, Ajinomoto Co, Inc, Kawasaki, Japan.
Yamamoto
H
H
Yoshimoto
R
R
D000800:Angioplasty, Balloon; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D020212:Carotid Artery Injuries / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005340:Fibrinogen / Q000032:analysis; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013927:Thrombosis / Q000276:immunology / Q000517:prevention & control*; D013997:Time Factors; D017539:Tunica Intima / Q000378:metabolism / Q000503:physiopathology; D014841:von Willebrand Factor / Q000032:analysis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D005340:Fibrinogen