Amyloid precursor protein 770 is specifically expressed and released from platelets
Amyloid precursor protein 770 is specifically expressed and released from platelets
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DOI：
10.1074/jbc.ra120.012904
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发表时间：
2020-09-18
影响因子：
4.8
通讯作者：
Kitazume, Shinobu
中科院分区：
文献类型：
--
作者：
Miura, Saori;Yoshihisa, Akiomi;Kitazume, Shinobu
血小板不仅在血管损伤后的止血中起重要作用，而且还参与冠状动脉疾病（CAD）和脑血管病变的发展。建议CAD和脑缺血患者接受抗血小板治疗，但其严重出血并发症的发生率增加。血小板活化状态的评估和抗血小板治疗的反应，在每个病人都是非常需要的。β-淀粉样前体蛋白（APP）770在血管内皮细胞中表达，其胞外区，APP 770的可溶形式（sAPP 770，也称为连接蛋白-2），被蛋白水解切割以脱落。丰富的sAPP 770也从活化的血小板释放。在这项研究中，我们使用来自CAD患者和对照受试者的外周血样本，并评估sAPP 770作为血小板活化的特异性生物标志物。首先，sAPP 770的血浆水平与可溶性形式CD 40配体（CD 40 L）的血浆水平相关性良好，CD 40 L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显示，CD 40 L表达在活化的T细胞中上调，而APP 770表达在除血小板外的所有血细胞类型中可忽略不计。在胶原或ADP刺激后，聚集的血小板立即释放sAPP 770。最后，双重抗血小板治疗的患者显示血浆sAPP 770水平显著低于未治疗的患者。总之，我们的数据表明，血浆sAPP 770可能是血小板活化的一个有前途的生物标志物。
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. beta-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.