Platelets not only play an essential role in hemostasis after vascular injury but are also involved in the development of coronary artery disease (CAD) and cerebrovascular lesions. Patients with CAD and cerebral ischemia are recommended to undergo antiplatelet therapy, but they have an increased incidence of major bleeding complications. Both assessment of the platelet activation status and response to antiplatelet therapy in each patient are highly desired. β-Amyloid precursor protein (APP) 770 is expressed in vascular endothelial cells, and its extracellular region, a soluble form of APP770 (sAPP770, also called nexin-2), is proteolytically cleaved for shedding. Abundant sAPP770 is also released from activated platelets. In this study, we used peripheral blood samples from patients with CAD and control subjects and evaluated sAPP770 as a specific biomarker for platelet activation. First, the plasma levels of sAPP770 correlated well with those of the soluble form CD40 ligand (CD40L), an established biomarker for platelet activation. Additionally, flow cytometry analysis using peripheral blood cells showed that CD40L expression is up-regulated in activated T cells, whereas APP770 expression is negligible in all blood cell types except platelets. Following stimulation with collagen or ADP, aggregating platelets immediately released sAPP770. Finally, patients with dual antiplatelet therapy showed significantly lower levels of plasma sAPP770 than those with no therapy. Taken together, our data show that plasma sAPP770 could be a promising biomarker for platelet activation.

中文翻译：

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淀粉样前体蛋白 770 从血小板中特异性表达和释放。

血小板不仅在血管损伤后止血中起重要作用，而且还参与冠状动脉疾病（CAD）和脑血管病变的发展。建议患有 CAD 和脑缺血的患者接受抗血小板治疗，但他们的大出血并发症发生率增加。非常需要评估每位患者的血小板活化状态和对抗血小板治疗的反应。β-淀粉样前体蛋白 (APP) 770 在血管内皮细胞中表达，其胞外区域，APP770 的可溶性形式（sAPP770，也称为 nexin-2），被蛋白水解裂解以脱落。大量的 sAPP770 也从活化的血小板中释放出来。在这项研究中，我们使用了来自 CAD 患者和对照受试者的外周血样本，并评估了 sAPP770 作为血小板活化的特异性生物标志物。首先，sAPP770 的血浆水平与可溶性形式 CD40 配体 (CD40L) 的血浆水平密切相关，CD40L 是血小板活化的既定生物标志物。此外，使用外周血细胞的流式细胞术分析表明，CD40L 表达在活化的 T 细胞中上调，而 APP770 表达在除血小板外的所有血细胞类型中都可以忽略不计。在用胶原蛋白或 ADP 刺激后，聚集的血小板立即释放 sAPP770。最后，接受双重抗血小板治疗的患者的血浆 sAPP770 水平显着低于未接受治疗的患者。总之，我们的数据表明血浆 sAPP770 可能是血小板活化的有希望的生物标志物。