Dong Jing-fei
Thrombosis Research Section, Baylor College of Medicine, Houston, TX 77030, USA.
Curr Opin Hematol. 2007 May;14(3):270-6. doi: 10.1097/MOH.0b013e3280d35820.
ADAMTS13 represents a landmark in a journey that began over 80 years ago with a single clinical case. Thrombotic thrombocytopenic purpura exemplifies how von Willebrand factor can be responsible for life-threatening thrombosis. This review summarizes recent progress on ADAMTS13, which prevents this deadly event.
Recent advances are summarized in four main areas. First, the core ADAMTS13-binding site is contained in a short sequence in the A2 domain, but other domains affect this interaction. Mutations from thrombotic thrombocytopenic purpura and von Willebrand disease provide clues for the structural prerequisites and regulation of von Willebrand factor cleavage. Second, studies are unraveling the reasons why urea, BaCl2, and low ionic strength are required to cleave von Willebrand factor under static conditions. Third, studies on thrombotic thrombocytopenic purpura and ADAMTS13-knockout mice suggest that ADAMTS13 deficiency alone may not be sufficient to cause thrombotic thrombocytopenic purpura. Finally, ADAMTS13 could be an antithrombotic agent for thrombotic thrombocytopenic purpura and other thrombotic conditions.
Study of ADAMTS13 has exploded since this metalloprotease was characterized. This knowledge reveals the nature of ADAMTS13's interaction with von Willebrand factor and the pathogenesis of clinical thrombotic thrombocytopenic purpura, especially in relation to ADAMTS13.
ADAMTS13代表了一段始于80多年前单个临床病例的历程中的一个里程碑。血栓性血小板减少性紫癜例证了血管性血友病因子如何导致危及生命的血栓形成。本综述总结了ADAMTS13的最新进展，它可预防这一致命事件。
最新进展主要总结为四个方面。第一，ADAMTS13的核心结合位点包含在A2结构域的一个短序列中，但其他结构域会影响这种相互作用。血栓性血小板减少性紫癜和血管性血友病的突变提供了血管性血友病因子裂解的结构前提和调控线索。第二，研究正在揭示在静态条件下裂解血管性血友病因子为何需要尿素、氯化钡和低离子强度。第三，对血栓性血小板减少性紫癜和ADAMTS13基因敲除小鼠的研究表明，仅ADAMTS13缺乏可能不足以导致血栓性血小板减少性紫癜。最后，ADAMTS13可能是治疗血栓性血小板减少性紫癜和其他血栓性疾病的抗血栓药物。
自从这种金属蛋白酶被鉴定以来，对ADAMTS13的研究呈爆发式增长。这些知识揭示了ADAMTS13与血管性血友病因子相互作用的本质以及临床血栓性血小板减少性紫癜的发病机制，尤其是与ADAMTS13相关的机制。
