Platelet CD36 surface expression levels affect functional responses to oxidized LDL and are associated with inheritance of specific genetic polymorphisms
Platelet CD36 surface expression levels affect functional responses to oxidized LDL and are associated with inheritance of specific genetic polymorphisms
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DOI：
10.1182/blood-2011-02-338582
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发表时间：
2011-06-09
期刊：
影响因子：
20.3
通讯作者：
Silverstein, Roy L.
中科院分区：
文献类型：
--
作者：
Ghosh, Arunima;Murugesan, Gurunathan;Silverstein, Roy L.
CD36 通过与氧化低密度脂蛋白 (oxLDL)、细胞源性微粒和血小板反应蛋白-1 结合来调节血小板功能。我们假设血小板 CD36 表达水平可能与特定基因多态性的遗传有关，并且这将决定血小板对 oxLDL 的反应性。对 500 多名受试者的分析表明，随着时间的推移，各个供体中的 CD36 表达水平是一致的，但供体之间差异很大（每个血小板 200-14 000 个分子）。对具有不同 CD36 表达水平的一组受试者进行的血小板聚集测定和流式细胞术显示，血小板对 oxLDL 的激活反应与 CD36 表达水平之间存在高度相关性 (r(2) = 0.87)。克利夫兰诊所 ASCLOGEN 研究中对 374 名白人受试者进行的全基因组关联研究表明，CD36 中的单核苷酸多态性与血小板表面 CD36 表达有很强的关联性。大多数这些发现在 25 名黑人受试者中得到了重复。一项创新的基于基因的全基因组扫描提供了进一步的证据，表明 CD36 中的单核苷酸多态性与 CD36 表达密切相关。这些研究表明，血小板上的 CD36 表达差异很大，与 oxLDL 的功能反应相关，并且与特定 CD36 基因多态性的遗传相关，并表明特定 CD36 多态性的遗传可能影响血栓形成风险。 （血。2011；117（23）：6355-6366）
CD36 modulates platelet function via binding to oxidized LDL (oxLDL), cell-derived microparticles, and thrombospondin-1. We hypothesized that the level of platelet CD36 expression may be associated with inheritance of specific genetic polymorphisms and that this would determine platelet reactivity to oxLDL. Analysis of more than 500 subjects revealed that CD36 expression levels were consistent in individual donors over time but varied widely among donors (200-14 000 molecules per platelet). Platelet aggregometry and flow cytometry in a subset of subjects with various CD36 expression levels revealed a high level of correlation (r(2) = 0.87) between platelet activation responses to oxLDL and level of CD36 expression. A genome-wide association study of 374 white subjects from the Cleveland Clinic ASCLOGEN study showed strong associations of single nucleotide polymorphisms in CD36 with platelet surface CD36 expression. Most of these findings were replicated in a smaller subset of 25 black subjects. An innovative gene-based genome-wide scan provided further evidence that single nucleotide polymorphisms in CD36 were strongly associated with CD36 expression. These studies show that CD36 expression on platelets varies widely, correlates with functional responses to oxLDL, and is associated with inheritance of specific CD36 genetic polymorphisms, and suggest that inheritance of specific CD36 polymorphisms could affect thrombotic risk. (Blood. 2011; 117(23): 6355-6366)