Effect of a Synthetic Peptide Corresponding to Residues 313 to 320 of the αIIbSubunit of the Human Platelet Integrin αIIbβ3on Carotid Artery Thrombosis in Rabbits
| Autor: | Lampros K. Michalis, Vassilios Tsikaris, Nikolaos D. Papamichael, Christos S. Katsouras, Anna Kotsia, Vassilios Moussis, Alexandros D. Tselepis, Eleni M. Stathopoulou, Loukas D. Tsironis, Vassiliki D. Roussa, Ruxandra-Maria Stanica |
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| Rok vydání: | 2009 |
| Předmět: |
Platelet Aggregation
Platelet Glycoprotein GPIIb-IIIa Complex Pharmacology medicine Animals Humans Platelet Carotid Artery Thrombosis Artery occlusion Thrombus Blood Coagulation Dose-Response Relationship Drug business.industry Fibrinogen binding medicine.disease Peptide Fragments Disease Models Animal Coagulation Anesthesia Carotid artery occlusion Molecular Medicine Rabbits business Oligopeptides Platelet Aggregation Inhibitors Ex vivo |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 329:634-640 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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