NEUTRALIZING ANTIBODIES DIRECTED AGAINST OSTEOPONTIN INHIBIT RAT CAROTID NEOINTIMAL THICKENING AFTER ENDOTHELIAL DENUDATION

Osteopontin is an arginine-glycine-aspartate-containing acidic glycopr otein with adhesive and migratory activities in vitro. We previously s howed that osteopontin was highly expressed in injured rat arteries as well as in human atherosclerotic plaques. In contrast, uninjured bloo d vessels make very little osteopontin. In this report, we have invest igated the role of osteopontin in rat neointima formation using neutra lizing antibodies. Rats were treated with either nonimmune or antioste opontin antibody and subjected to endothelial denudation of the caroti d artery by using a balloon catheter. Two weeks after injury, intimal areas and cell numbers were significantly decreased (33% and 31%, resp ectively) in the antiosteopontin group compared with the nonimmune IgG group. No differences in carotid medial areas or cell numbers were ob served. Intimal and medial replication rates, as measured by continuou s bromodeoxyuridine infusion during the final week of the experimental protocol, were not significantly different between the two groups. No gross histological changes were noted in the intimas formed in the pr esence of either neutralizing or nonimmune antibody. In addition, no d ifference in early carotid medial cell replication rate was observed w hen antibodies were infused for 4 days after angioplasty. These data d emonstrate for the first time a functional role for osteopontin in the process of carotid neointimal thickening in vivo and suggest that ost eopontin plays an active role in the remodeling processes important fo r human atherosclerotic and restenotic lesion development.