Non‐antiplatelet effect of clopidogrel: improving endothelial function in Chinese healthy subjects with different CYP2C19 genotype
Non‐antiplatelet effect of clopidogrel: improving endothelial function in Chinese healthy subjects with different CYP2C19 genotype
复制标题
DOI：
10.1111/1440-1681.12325
复制
发表时间：
2015-01
影响因子：
2.9
通讯作者：
Yinzhuang Zhang;Bi-Lian Chen;Wei Zhang;Xing-zhi Cao
中科院分区：
文献类型：
--
作者：
Yinzhuang Zhang;Bi-Lian Chen;Wei Zhang;Xing-zhi Cao
氯吡格雷已被证明可以改善体外和冠状动脉疾病患者的内皮功能。然而，目前尚不清楚氯吡格雷的这种作用是否与决定氯吡格雷抗血小板作用的CYP2C19多态性有关。基因分型后，12名健康参与者被纳入研究。其中CYP2C19*1/*1（广泛代谢者；EM） 6例，CYP2C19*2/*2或*3（代谢不良者；PM） 6例。所有参与者口服氯吡凝胶300毫克。通过测量肱动脉血流介导的扩张来评估内皮功能，并在给药300 mg氯吡格雷后0、4和24小时用光学聚集法测定二磷酸腺苷诱导的血小板聚集。CYP2C19 EM组和PM组在氯吡格雷负荷剂量给药后4和24小时，血流介导的舒张明显升高，但两组间无显著差异。CYP2C19 EM组在氯吡格雷给药后4和24小时，二磷酸腺苷诱导的血小板聚集明显受到抑制。然而，在两个CYP2C19组中，血流介导的舒张变化与二磷酸腺苷诱导的血小板聚集之间没有统计学相关性。本研究首次报道氯吡格雷改善中国健康受试者内皮功能，且与CYP2C19基因型无关，与抗血小板作用无关。
Clopidogrel has been shown to improve endothelial function in vitro and in patients with coronary artery disease. However, it remains unclear whether such an effect of clopidogrel is associated with CYP2C19 polymorphisms that determine the antiplatelet effect of clopidogrel. After genotyping, 12 healthy participants were enrolled in the study. Among them, six participants were CYP2C19*1/*1 (extensive metabolizers; EM) and the other six participants were CYP2C19*2/*2 or *3 (poor metabolizers; PM). All participants received 300 mg clopidogel orally. Endothelial function was assessed by measurement of flow‐mediated dilation of the brachial artery, and adenosine diphosphate‐induced platelet aggregation was determined by using optical aggregometry at 0, 4 and 24 h after administration of 300 mg clopidogrel. Flow‐mediated dilation was significantly higher at 4 and 24 h after a loading‐dose administration of clopidogrel in both the CYP2C19 EM and PM groups, but showed no significant difference between the two groups. Adenosine diphosphate‐induced platelet aggregation was significantly inhibited at 4 and 24 h after administration of clopidogrel in the CYP2C19 EM group. However, there was no statistical correlation between the change in flow‐mediated dilation and adenosine diphosphate‐induced platelet aggregation in the two CYP2C19 groups. This is the first study to report that clopidogrel improves endothelial function in healthy Chinese subjects, which is unrelated with the CYP2C19 genotype and independent of antiplatelet action.