INHIBITION OF INTEGRIN FUNCTION BY A CYCLIC RGD-CONTAINING PEPTIDE PREVENTS NEOINTIMA FORMATION

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).