Verweij C L
Department of Molecular Biology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Haemostasis. 1988;18(4-6):224-45. doi: 10.1159/000215810.
Endothelium forms the inner lining of all blood vessels and, as a consequence, is in direct contact with the blood. Because of this and the synthesis and secretion of hemostatic components, the endothelium is able to modulate coagulation and fibrinolysis. An important hemostatic factor synthesized by endothelial cells is the von Willebrand factor (vWF). vWF is a large plasma glycoprotein which promotes the adhesion of platelets to the vessel wall after a vascular injury. vWF is initially synthesized as a pre-pro-polypeptide. During its transport to the outside of the cell, the single-chain polypeptides are assembled into multimers. The pro-polypeptide can be cleaved and also be secreted. Free pro-polypeptide is identified as von Willebrand antigen II, a plasma glycoprotein of unknown function. Plasma vWF consists of a heterogenous series of multimers, composed of an apparently single-type glycoprotein subunit, linked together by disulfide bonds. The hemostatic potency of vWF was shown to increase with increasing multimer size. Therefore, the multimeric assembly of vWF is a crucial aspect in vWF biosynthesis. Furthermore, vWF synthesized by endothelial cells can either be secreted constitutively or stored and released upon stimulation of the endothelial cell. In this review, data are presented which contribute to the understanding of the biosynthetic pathway and complex processing which vWF has to undergo before it is secreted by the endothelial cell. These data have allowed a prediction of the sequential events underlying vWF biosynthesis, processing, multimer assembly, and secretion.
内皮细胞构成所有血管的内层，因此与血液直接接触。鉴于此以及其对止血成分的合成与分泌，内皮细胞能够调节凝血和纤维蛋白溶解过程。内皮细胞合成的一种重要止血因子是血管性血友病因子（vWF）。vWF是一种大型血浆糖蛋白，在血管损伤后可促进血小板黏附于血管壁。vWF最初作为前原多肽进行合成。在其转运至细胞外的过程中，单链多肽组装成多聚体。前多肽可被切割并分泌。游离的前多肽被鉴定为血管性血友病抗原II，这是一种功能未知的血浆糖蛋白。血浆vWF由一系列异源多聚体组成，这些多聚体由一种明显单一类型的糖蛋白亚基构成，通过二硫键连接在一起。研究表明，vWF的止血效力随多聚体大小增加而增强。因此，vWF的多聚体组装是其生物合成中的一个关键环节。此外，内皮细胞合成的vWF既可以组成型方式分泌，也可以在内皮细胞受到刺激时储存并释放。在这篇综述中，呈现了有助于理解vWF在由内皮细胞分泌之前必须经历的生物合成途径和复杂加工过程的数据。这些数据使得人们能够预测vWF生物合成、加工、多聚体组装和分泌过程中相继发生的事件。
