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Titolo:
Effects of ticlopidine on von Willebrand factor-mediated shear-induced platelet activation and aggregation
Autore:
Goto, S; Tamura, N; Sakakibara, M; Ikeda, Y; Handa, S;
Indirizzi:
Tokai Univ, Sch Med, Dept Med, Div Cardiol, Kanagawa 2591193, Japan Tokai Univ Kanagawa Japan 2591193 , Div Cardiol, Kanagawa 2591193, Japan Keio Univ, Sch Med, Dept Med, Tokyo 160, Japan Keio Univ Tokyo Japan 160Keio Univ, Sch Med, Dept Med, Tokyo 160, Japan
Titolo Testata:
PLATELETS
fascicolo: 7, volume: 12, anno: 2001,
pagine: 406 - 414
SICI:
0953-7104(200111)12:7<406:EOTOVW>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE MYOCARDIAL-INFARCTION; VONWILLEBRAND-FACTOR-BINDING; ACUTE CORONARY SYNDROMES; GLYCOPROTEIN-IB; P-SELECTIN; MONOCLONAL-ANTIBODY; SURFACE EXPRESSION; THROMBUS FORMATION; ANTIPLATELET DRUG; MOLECULAR-BASIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Goto, S Tokai Univ, Sch Med, Dept Med, Div Cardiol, 143 Shimokasuya, Kanagawa 2591193, Japan Tokai Univ 143 Shimokasuya Kanagawa Japan 2591193 2591193, Japan
Citazione:
S. Goto et al., "Effects of ticlopidine on von Willebrand factor-mediated shear-induced platelet activation and aggregation", PLATELETS, 12(7), 2001, pp. 406-414

Abstract

Ticlopidine, recently classified as a P2Y(12) ADP receptor blockade, is known to be an effective antiplatelet agent preventing arterial thrombosis, e.g., myocardial infarction or cerebral infarction, but the mechanism of thein vivo antithrombotic effects of ticlopidine is not fully understood. Blood was drawn from seven normal volunteers before and 7 days after consecutive intake of ticlopidine, and 1 day after oral intake of aspirin after 7 days of ticlopidine wash-out period. Effects of drug intake on shear-induced von Willebrand factor (vWF) binding to platelets, platelet activation evidenced by P-selectin surface expression and translocation of GP Iba, and vWF-mediated platelet aggregation, were investigated by using an optically modified cone-plate viscometer and quantitative flow cytometry. The maximum extent of platelet aggregation occurring under a high shear rate of 10800 s(-1), presumably mediated by vWF, was not significantly influenced by either ticlopidine or aspirin. However, significant dissociation of once aggregatedplatelets occurred in samples obtained after ticlopidine intake (25.4 +/-9.3%, P=0.00030) and less significantly after aspirin intake (15.9 +/-5.7%, P=0.0013), while only insignificant and modest dissociation occurred in controls (6.3 +/-4.4%, n.s.). Binding experiments also revealed that the shear-induced vWF binding to platelets was significantly inhibited by ticlopidine, and less significantly by aspirin, although other indicators of plateletactivation, such as shear-induced P-selectin expression and GP Ib alpha translocation were not influenced by either ticlopidine or aspirin. We demonstrate here that platelet aggregation mediated by von Willebrand factor (vWF) under a high shear rate of 10800 s(-1) cannot be stabilized and that dissociation occurs readily when ADP receptor stimulation is blocked by continuous intake of ticlopidine, indicating that these effects on platelet thrombus formation may contribute to the in vivo antithrombotic effects of ticlopidine.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 00:49:19