Impact of variables of the P-selectin - P-selectin glycoprotein ligand-1 axis on leukocyte-platelet interactions in cardiovascular disease
Impact of variables of the P-selectin - P-selectin glycoprotein ligand-1 axis on leukocyte-platelet interactions in cardiovascular disease
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DOI：
10.1160/th14-08-0690
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发表时间：
2015-04-01
影响因子：
6.7
通讯作者：
Panzer, Simon
中科院分区：
文献类型：
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作者：
Gremmel, Thomas;Koppensteiner, Renate;Panzer, Simon
白细胞-血小板聚集体 (LPA) 通过 P-选择素 P-选择素糖蛋白配体 (PSGL)-1 轴形成，在动脉粥样硬化血栓形成中发挥着关键作用。为了研究血小板 (pP-选择素) 和可溶性 P-选择素 (sP-选择素) 以及编码 P-选择素 (SELP) 和 PSGL-1 (SELPLG) 的基因变异对 LPA 形成的影响，我们通过流式细胞术评估了 263 名接受血管成形术和支架置入术的患者的单核细胞 (MPA) 和中性粒细胞血小板聚集体 (NPA) 以及 pP-选择素。通过ELISA测定sP-选择素，通过等位基因特异性PCR测定SELP Pro715等位基因和SELPLG Ile62等位基因。 Pro715等位基因与体内pP-选择素和sP-选择素的较低水平显着相关，而激动剂的诱导型pP-选择素不受Pro715等位基因的影响。 PP-选择素与 MPA 和 NPA 的形成显着相关。 MPA 和 NPA 的体内形成分别取决于体内 pP-选择素的 19% 和 7.4%，无论 Pro715 等位基因和 Ile62 等位基因携带状态如何。 TRAP-6 诱导型 MPA 和 NPA 分别依赖于 TRAP-6 诱导型 pP-选择素的 34% 和 27%，但与 Pro715 等位基因携带状态无关。与非携带者相比，Ile62 等位基因的携带者显示 TRAP-6 诱导型 pP-选择素和 TRAP-6 诱导型 MPA/NPA 之间的相关性更强。此外，Ile62 等位基因携带者中 TRAP-6 诱导的 NPA 较高，这表明凝血酶敏感性较高。总之，我们的研究结果表明 pP-选择素对 MPA 和 NPA 形成具有重要作用，而 sP-选择素、SELP Pro715 等位基因和 SELPLG Ile62 等位基因等其他变量影响较小。
The formation of leukocyte-platelet aggregates (LPA), through the P-selectin P-selectin glycoprotein ligand (PSGL)-1 axis, plays a pivotal role in atherothrombosis. In order to investigate the influence of platelet (pP-selectin) and soluble P-selectin (sP-selectin), and of variations in the genes encoding for P-selectin (SELP) and PSGL-1 (SELPLG) on LPA formation, we assessed monocyte (MPA)- and neutrophil-platelet aggregates (NPA) as well as pP-selectin by flow cytometry in 263 patients undergoing angioplasty and stenting. sP-selectin was determined by ELISA, the SELP Pro715 allele and the SELPLG Ile62 allele were determined by allele specific PCR. The Pro715 allele was significantly associated with lower levels of in vivo pP-selectin and sP-selectin, while agonists' inducible pP-selectin was not influenced by the Pro715 allele. PP-selectin was significantly associated with MPA and NPA formation. The in vivo formation of MPA and NPA depended to 19% and 7.4%, respectively, on in vivo pP-selectin, irrespective of the Pro715 allele and the Ile62 allele carrier status. TRAP-6 inducible MPA and NPA depended to 34% and 27%, respectively, on TRAP-6 inducible pP-selectin, but were independent of the Pro715 allele carrier status. Carriers of the Ile62 allele showed a stronger correlation between TRAP-6 inducible pP-selectin and TRAP-6 inducible MPA/NPA than non-carriers. Furthermore, TRAP-6 inducible NPA were higher in Ile62 allele carriers, which suggests higher thrombin sensitivity. In conclusion, our findings point to the significant role of pP-selectin for MPA and NPA formation, while other variables like sP-selectin, the SELP Pro715 allele and the SELPLG Ile62 allele have less influence.