Effect of a Synthetic Peptide Corresponding to Residues 313 to 320 of the alpha(IIb) Subunit of the Human Platelet Integrin alpha(IIb)beta(3) on Carotid Artery Thrombosis in Rabbits (Journal article)

Papamichael, N. D./ Stathopoulou, E. M./ Roussa, V. D./ Tsironis, L. D./ Kotsia, A. P./ Stanica, R. M./ Moussis, V./ Tsikaris, V./ Katsouras, C. S./ Tselepis, A. D./ Michalis, L. K.


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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας
Keywords: fibrinogen gamma-chain,glycoprotein-iib-iiia,ligand recognition,binding,receptor,adhesion,activation,sequence,complex,plasma
URI: http://olympias.lib.uoi.gr/jspui/handle/123456789/10463
ISSN: 0022-3565
Link: <Go to ISI>://000265444000026
http://jpet.aspetjournals.org/content/329/2/634.full.pdf
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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