Dichotomous effects of exposure to bivalirudin in patients undergoing percutaneous coronary intervention on protease-activated receptor-mediated platelet activation.
Dichotomous effects of exposure to bivalirudin in patients undergoing percutaneous coronary intervention on protease-activated receptor-mediated platelet activation.
复制标题
接受经皮冠状动脉介入治疗的患者暴露于比伐卢定对蛋白酶激活受体介导的血小板活化的二分效应。
DOI：
10.1007/s11239-012-0812-9
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发表时间：
2013
影响因子：
4
通讯作者：
Cleator,JohnH
中科院分区：
文献类型：
--
作者：
Holinstat,Michael;Colowick,NancyE;Hudson,WillieJ;Blakemore,Dana;Chen,Qingxia;Hamm,HeidiE;Cleator,JohnH
比伐卢定是一种直接凝血酶抑制剂，越来越多地用于经皮冠状动脉介入治疗 (PCI)，之前已被证明缺乏固有的血小板活化作用。凝血酶通过激活人血小板上的蛋白酶激活受体 1 (PAR1) 和 PAR4 发挥作用，启动导致血小板聚集的信号级联反应。尽管比伐卢定的使用越来越多，但其对血小板功能的影响尚未明确。因此，通过 PAR1 和 PAR4 评估 PCI 期间比伐卢定暴露对洗涤血小板功能的潜在短期影响。 Bivalirudin 显着抑制低剂量凝血酶介导的血小板聚集、致密颗粒分泌、整合素 αIIbβ3 激活和 Rap1 激活以及高剂量凝血酶介导的致密颗粒分泌和 Rap1 激活。暴露于比伐卢定不会改变 PAR1 或 4 激动剂肽（PAR1-AP 或 PAR4-AP）诱导的聚集、致密颗粒分泌、整合素糖蛋白 IIbIIIa 激活或 Rap1 激活。然而，在高剂量凝血酶和 PAR1-AP 以及低剂量和高剂量 PAR4-AP 刺激后，暴露于比伐卢定显着增强了 P-选择素的表面表达。因此，我们的数据首次表明，在某些条件下，接触比伐卢定会增加 P-选择素的表达，证明比伐卢定可以增加固有的血小板活性。
Bivalirudin is a direct thrombin inhibitor that is increasingly used in percutaneous coronary intervention (PCI) and has been previously shown to lack inherent platelet activation. Thrombin works through activation of protease activated receptor-1 (PAR1) and PAR4 on human platelets to initiate signaling cascades leading to platelet aggregation. Despite the increasing usage of bivalirudin, the effects on platelet function have not been well defined. Bivalirudin exposure during PCI was therefore assessed for its potential short-term effects on washed platelet function through PAR1 and PAR4. Bivalirudin significantly inhibited low-dose thrombin-mediated platelet aggregation, dense granule secretion, integrin αIIbβ3 activation and Rap1 activation and high dose thrombin-mediated dense granule secretion and Rap1 activation. Exposure to bivalirudin did not alter PAR1 or 4 agonist peptide (PAR1-AP or PAR4-AP) induced aggregation, dense granule secretion, integrin glycoprotein IIbIIIa activation or Rap1 activation. However, exposure to bivalirudin significantly potentiated surface expression of P-selectin following stimulation with high dose thrombin and PAR1-AP, and both low and high dose PAR4-AP. Hence, our data are the first to show that exposure to bivalirudin increased P-selectin expression with certain conditions demonstrating that bivalirudin can increase inherent platelet activity.