Effects of endothelial nitric oxide synthase gene polymorphisms on platelet function, nitric oxide release, and interactions with estradiol.
Effects of endothelial nitric oxide synthase gene polymorphisms on platelet function, nitric oxide release, and interactions with estradiol.
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DOI：
10.1097/00008571-200207000-00008
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发表时间：
2002-07
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影响因子：
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通讯作者：
J. Tanus-Santos;Mehul Desai;Leslie R. Deak;J. Pezzullo;D. Abernethy;D. Flockhart;J. Freedman
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文献类型：
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作者：
J. Tanus-Santos;Mehul Desai;Leslie R. Deak;J. Pezzullo;D. Abernethy;D. Flockhart;J. Freedman
受损的血小板源性一氧化氮（NO）通过促进血小板募集和血栓形成而导致急性冠状动脉综合征。内皮型一氧化氮合酶（eNOS）基因的多态性变体与心血管疾病相关。为了检测eNOS变异体是否影响血小板源性NO和血小板功能，并评估雌二醇对血小板功能的影响，我们研究了47名健康高加索人的血小板，这些人在启动子区（T-786 C）、内含子4和外显子7（Glu 298 Asp）进行eNOS多态性基因分型。在对照样品和用17-α-雌二醇（10 nmol/l）预处理的样品中测量血小板聚集、血小板衍生的NO和超氧化物的产生。启动子区（P = 0.002）或外显子7（P = 0.007）变异的发生与较低水平的血小板源性NO相关（P > 0.05）。在启动子区变异的受试者中观察到超氧化物释放增加（P = 0.047），但在其他eNOS遗传变异的受试者中没有观察到。eNOS基因多态性对ADP诱导的血小板聚集无影响（P > 0.05）。然而，雌二醇显着增加血小板聚集（P = 0.004），和血小板衍生的超氧化物（P = 0.047）在外显子7的变异纯合子的个人，但没有在其他基因型的主题。这些数据表明，在启动子区和外显子7中的eNOS变体减少血小板源性NO，雌二醇显着增加血小板聚集纯合子外显子7中的变体，但不是在其他基因型的受试者，这表明eNOS变体可能会影响血栓形成的反应。
Impaired platelet-derived nitric oxide (NO) contributes to acute coronary syndromes by enhancing platelet recruitment and thrombus formation. Polymorphic variants of the endothelial NO synthase (eNOS) gene have been associated with cardiovascular diseases. To examine whether eNOS variants affect platelet-derived NO and platelet function, and to assess the effects of estradiol on platelet function, we studied platelets from 47 healthy caucasians who were genotyped for eNOS polymorphisms in the promoter region (T-786 C), in intron 4, and in exon 7 (Glu298Asp). Platelet aggregation, platelet-derived NO and superoxide production were measured in control samples and samples pretreated with 17-alpha-estradiol (10 nmol/l). The occurrence of variants in the promoter region (P = 0.002) or in exon 7 (P = 0.007), but not in intron 4 (P > 0.05), were associated with lower levels of platelet-derived NO. An increased (P = 0.047) release of superoxide was observed with platelets from subjects with the variant in the promoter region, but not with other eNOS genetic variants. The eNOS gene polymorphisms did not affect ADP-induced platelet aggregation (P > 0.05). However, estradiol significantly increased platelet aggregation (P = 0.004), and platelet-derived superoxide (P = 0.047) in individuals homozygous for the variant in exon 7, but not in subject with other genotypes. These data demonstrate that the eNOS variants in the promoter region and in exon 7 decrease platelet-derived NO and that estradiol significantly increases platelet aggregation in homozygous for the variant in exon 7 but not in subjects with other genotypes, suggesting that eNOS variants may influence the thrombotic response.