EFFECT OF KAPPA-CASEIN SPLIT PEPTIDES ON PLATELET-AGGREGATION AND ON THROMBUS FORMATION IN THE GUINEA-PIG

Citation
Cb. Sollier et al., EFFECT OF KAPPA-CASEIN SPLIT PEPTIDES ON PLATELET-AGGREGATION AND ON THROMBUS FORMATION IN THE GUINEA-PIG, Thrombosis research, 81(4), 1996, pp. 427-437
Citations number
21
Categorie Soggetti
Hematology,"Cardiac & Cardiovascular System","Peripheal Vascular Diseas
Journal title
ISSN journal
00493848
Volume
81
Issue
4
Year of publication
1996
Pages
427 - 437
Database
ISI
SICI code
0049-3848(1996)81:4<427:EOKSPO>2.0.ZU;2-G
Abstract
An undecapeptide (residues 106-116 of cow K-casein) is known to inhibi t human platelet aggregation and fibrinogen binding through inhibition of the interaction between the fibrinogen gamma-chain C-terminus and alpha(IIb)beta(3). This was due to structural homologies with the fibr inogen gamma-chain C-terminal dodecapeptide. We have therefore compare d in this work the in vitro anti-aggregating activity of kappa-casein split peptides and their in vivo potential antithrombotic activity in a model of arterial thrombosis triggered by laser-induced intimal inju ry in the guinea-pig. Caseinoglycopeptide (residues 106-169), the unde capeptide (residues 106-116) and the pentapeptide KNQDK (residues 112- 116) from cow K-casein, were anti-aggregating peptides and exerted a s ignificant antithrombotic activity in the guinea-pig. Caseinoglycopept ides from three species (cow, ewe and human) were also antithrombotic and the most potent being the human one. The antithrombotic activity w as achieved in vivo for doses less than the one suspected from in vitr o data and for which, ex vivo platelet aggregation was not decreased. In conclusion, the relative involvement of the fibrinogen gamma-chain C-terminal dodecapeptide could be much more important in in vivo throm bosis process than in in vitro platelet aggregation. Its specificity a nd activity in vivo unveiled an interesting potential way for inhibiti on of arterial thrombosis if alternative molecular presentation (i.e. peptidomimetics) and alternative route (i.e. per os) can be developed.