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Inhibition of neointima formation by a nonpeptide α v β 3 integrin receptor antagonist in a rabbit cuff model
Author(s) -
Racanelli Adrienne L.,
Gibbs Sandra K.,
Schlingmann Karen L.,
Corjay Martha H.,
Jadhav Prabhakar K.,
Reilly Thomas M.
Publication year - 2000
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(20000501)77:2<213::aid-jcb5>3.0.co;2-t
Subject(s) - neointima , antagonist , cuff , chemistry , integrin , receptor antagonist , receptor , pharmacology , medicine , endocrinology , surgery , restenosis , stent
This study was performed to determine whether a highly selective nonpeptide α v β 3 antagonist (SH306) would prove effective in inhibiting neointima 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 control group, was noted (0.20 vs 0.36 [n = 4]). A significant increase in the area 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 between 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 inhibition of GPIIb/IIIa was observed in SH306‐treated animals, as compared with the vehicle control group. We conclude that selective inhibition of α v β 3 reduced neointima formation in a rabbit model at 3 weeks. J. Cell. Biochem. 77:213–220, 2000. © 2000 Wiley‐Liss, Inc.