Inhibition of neointima formation by a nonpeptide alpha(v)beta(3) integrinreceptor antagonist in a rabbit cuff model

This study was performed to determine whether a highly selective nonpeptide alpha(v)beta(3) antagonist (SH306) would prove effective in inhibiting neo intima formation in a rabbit cuff model. The animals were dosed with SH306, 5 mg/kg i.v., followed by 10 mg/kg s.c., 3 times daily for 3 days, or with vehicle (10% DMAC). Rabbits were sacrificed and perfused on days 1, 3, and 21; the vessels were paraffin embedded. A reduction in the intima/media (I /M) of the SH306-treated rabbits, as compared with the vehicle-treated cont rol group, was noted (0.20 vs 0.36 [n = 4]) A significant increase in the a rea of the media was observed in the SH306-treated group versus the control group (0.20 vs 0.13). No difference was observed in cell proliferation bet ween SH306 and vehicle after 1-day and 3-day dosing. Thrombi were found in 43% of the control vessels and in only 14% of the drug-treated vessels. No anticoagulant was used during the surgical procedure. No increase in inhibi tion of GPIIb/IIIa was observed in SH306-treated animals, as compared with the vehicle control group. We conclude that selective inhibition of alpha(v )beta(3) reduced neointima formation in a rabbit model at 3 weeks. (C) 2000 Wiley-Liss, Inc.