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CARDIOVASCULAR

Effect of a Synthetic Peptide Corresponding to Residues 313 to 320 of the _IIb Subunit of the Human Platelet Integrin _IIbβ₃ on Carotid Artery Thrombosis in Rabbits

Medical School, Departments of Cardiology (N.D.P., V.D.R., A.P.K., C.S.K., L.K.M.) and Chemistry (E.M.S., L.D.T., R.-M.S., V.M., V.T., A.D.T.), University of Ioannina, Ioannina, Greece

The platelet integrin receptor _IIbβ₃ plays a critical role in thrombosis. We have shown previously that the octapeptide YMESRADR, corresponding to sequences 313 to 320 of the human _IIb subunit, inhibits human platelet activation and fibrinogen binding to _IIbβ₃, possibly interacting with the ligand. We investigated the effect of YMESRADR on electrically induced carotid artery thrombosis in New Zealand white rabbits. Peptide was administered via the femoral vein, starting 60 min before and continuing for 90 min after the electrical stimulation. Carotid blood flow was monitored for 90 min after the electrical stimulation. The peptide effects on platelet aggregation, in vitro and ex vivo, and on various coagulation, bleeding, and hemostatic parameters were evaluated. YMESRADR significantly inhibited rabbit platelet aggregation in vitro in a dose-dependent manner. It is important that peptide administration in vivo, at doses ranging from 3 to 15 mg/kg, prolonged the duration of the patency of the carotid artery, and no artery occlusion was observed until the end of the study (90 min after electrical stimulation). Furthermore, YMESRADR administration reduced platelet aggregation ex vivo and thrombus weight; however, these reductions reached statistical significance, compared with the control group, at the peptide doses of 12 and 15 mg/kg. YMESRADR did not affect any coagulation parameter studied and the hemostatic response observed in control animals. Thus, YMESRADR represents a novel antiplatelet agent that can inhibit thrombus formation effectively and carotid artery occlusion without causing hemorrhagic complications in a rabbit model of arterial thrombosis.

Address correspondence to: Dr. Alexandros D. Tselepis, Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. E-mail: atselep{at}uoi.gr