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Circulation, Vol 90, 2203-2206, Copyright © 1994 by American Heart Association
H Matsuno, JM Stassen, J Vermylen and H Deckmyn
BACKGROUND--RGD-containing peptides are able to prevent binding of ligands
to certain integrins such as alpha IIb beta 3 (glycoprotein IIb/IIIa) and
alpha v beta 3 and as such are inhibitors for platelet aggregation and
smooth muscle cell migration, both of which are involved in neointima
formation. METHODS AND RESULTS--Hamster carotid arteries were damaged, and
neointima formation was determined at different time points. G4120, a
cyclic RGD-containing peptide, was administered continuously intravenously
by an implanted osmotic pump. Neointima formation was inhibited dose
dependently. The inhibition was strongest when treatment was started before
the vascular injury and continued for the full observation period.
Treatment started after the damage and maintained until neointima
assessment or started before and stopped earlier was less effective.
CONCLUSIONS--Inhibition of integrin function by an RGD-containing peptide
results in reduction of the development of a neointima. This effect is due
both to an early event, which could be due to inhibition of secretion of
PDGF by the platelets with blocked alpha IIb beta 3, and to a late event,
possibly by interference with smooth muscle cell alpha v beta 3.
ARTICLES
Inhibition of integrin function by a cyclic RGD-containing peptide prevents neointima formation
Center for Molecular and Vascular Biology, K.U. Leuven, Belgium.
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