期刊
THROMBOSIS AND HAEMOSTASIS
卷 103, 期 6, 页码 1210-1217出版社
SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
DOI: 10.1160/TH09-11-0770
关键词
Platelet; P2Y(12); thienopyridines; receptor blockade; ADP
资金
- British Heart Foundation [PG/03/100]
- Daiichi Sankyo Co., Ltd.
- Eli Lilly and Company
The thienopyridine P2Y(12) receptor antagonists clopidogrel and prasugrel prevent arterial thrombosis and are routinely used following percutaneous coronary intervention. However, the optimal level of P2Y(12) blockade to effectively inhibit platelet function is unknown. These studies utilised the active metabolite of prasugrel (R-138727) to achieve a range of P2Y(12) blockade in vitro and assessed several aspects of platelet function. Blood from healthy volunteers was incubated with R-138727 (0-10 mu M). P2Y(12) receptor number was assessed using a P-33-2MeSADP binding assay. Platelet aggregation (PA) was measured by optical aggregometry with ADP 2-20 mu M. VASP phosphorylation, annexin V binding, microparticle formation and P-selectin expression were assessed by flow cytometry. Increasing numbers of unblocked receptors were required for a sustained aggregation response with decreasing concentrations of ADP. A P2Y(12) receptor blockade of 60-80% resulted in strong inhibition of final PA response, P-selectin expression, microparticle formation and vasodilator-stimulated phosphoprotein (VASP). PA induced by ADP 2 mu M and P-selectin expression were particularly sensitive to low levels of receptor blockade whereas the VASP phosphorylation assay was relatively insensitive, requiring 60% receptor blockade to achieve substantial inhibition. Different assays varied in their ability to discriminate particular ranges of P2Y(12) blockade and 80% or greater P2Y(12) receptor blockade is required for consistently strong inhibition of several aspects of platelet function. These data guide the interpretation of results from different assays used to monitor the effects of P2Y(12) receptor antagonists.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据