The platelet
integrin receptor alpha(IIb)beta(3) plays a critical role in
thrombosis. We have shown previously that the octapeptide YMESRADR, corresponding to sequences 313 to 320 of the human alpha(IIb) subunit, inhibits human platelet activation and
fibrinogen binding to alpha(IIb)beta(3), 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.