title: Non-antiplatelet effect of clopidogrel: improving endothelial function in Chinese healthy subjects with different CYP2C19 genotype.
abstract: 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.
authors.affiliation: Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yin-Zhuang
authors.initials: YZ
authors.lastname: Zhang
authors.forename: Bi-Lian
authors.initials: BL
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005838:Genotype; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: CYP2C19 genotype; clopidogrel; endothelial function; flow-mediated dilation