Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Semin Thromb Hemost. 2014 Feb;40(1):28-33. doi: 10.1055/s-0033-1363156. Epub 2013 Dec 13.
Platelet-vessel wall interaction is mediated by von Willebrand factor (VWF), which thereby plays a major role in physiological hemostasis and thrombotic disease. VWF is released as ultralarge multimers from endothelial cells, whereupon it is cleaved by ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type I repeats-13). The prohemostatic properties of VWF are dependent of its multimeric size; hence, ADAMTS13 activity is an important determinant in platelet-vessel wall interaction. Deficiency of ADAMTS13 in its most classical form in thrombotic thrombocytopenic purpura can lead to severe thrombotic microangiopathy. However, there is a growing variety of diseases in which ADAMTS13 levels have been found to be decreased and in which reduced cleavage of VWF may play a role. Hence, targeting of VWF cleavage by pharmacological modulation of ADAMTS13 levels is an interesting approach in some of these conditions. This review discusses the available evidence for a role of ADAMTS13 in various disease states and the potential therapeutic benefit of restoration of ADAMTS13 levels.
血小板-血管壁相互作用由血管性血友病因子（von Willebrand factor，VWF）介导，VWF 在生理性止血和血栓性疾病中起着重要作用。VWF 从血管内皮细胞以超大多聚体形式释放，随后被 ADAMTS13（含血小板反应蛋白 1 型重复的解整合素金属蛋白酶 13）切割。VWF 的促凝特性与其多聚体大小有关；因此，ADAMTS13 活性是血小板-血管壁相互作用的重要决定因素。最经典形式的 ADAMTS13 缺乏可导致血栓性血小板减少性紫癜的严重血栓性微血管病。然而，越来越多的疾病发现 ADAMTS13 水平降低，VWF 的切割减少可能发挥作用。因此，通过药理学调节 ADAMTS13 水平来靶向 VWF 切割是这些疾病的一种有前途的治疗方法。本文综述了 ADAMTS13 在各种疾病状态中的作用以及恢复 ADAMTS13 水平的潜在治疗益处的相关证据。
