Chen Xin, Cheng Xin, Zhang Shufan, Wu Danhong
Department of Neurology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Front Neurol. 2019 Jul 17;10:772. doi: 10.3389/fneur.2019.00772. eCollection 2019.
Thrombosis is the predominant underlying mechanism of acute ischemic stroke (AIS). Though thrombolysis with tPA has been proven to be effective in treating AIS within the time window, the majority of AIS patients fail to receive tPA due to various reasons. Current medical therapies for AIS have limited efficacy and pose a risk of intracerebral hemorrhage. ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) is a metalloprotease that effectively breaks down the von Willebrand Factor (VWF), a key factor in thrombus formation. Previous studies have proven that dysfunction of ADAMTS13 is associated with many diseases. Recently, ADAMTS13 has been reported to be closely related to stroke. In this review, we briefly described the structure of ADAMTS13 and its role in thrombosis, inflammation, as well as angiogenesis. We then focused on the relationship between ADAMTS13 and AIS, ranging from ischemic stroke occurrence, to AIS treatment and prognosis. Based on research findings from , animal, and clinical studies, we propose that ADAMTS13 is a potential biomarker to guide appropriate treatment for ischemic stroke and a promising therapeutic agent for tPA resistant thrombi.
血栓形成是急性缺血性卒中(AIS)的主要潜在机制。尽管使用组织型纤溶酶原激活剂(tPA)进行溶栓已被证明在时间窗内治疗AIS有效,但由于各种原因,大多数AIS患者未能接受tPA治疗。目前针对AIS的药物治疗疗效有限,且存在脑出血风险。含Ⅰ型血小板反应蛋白基序的解聚素样金属蛋白酶13(ADAMTS13)是一种金属蛋白酶,可有效分解血管性血友病因子(VWF),后者是血栓形成的关键因素。既往研究已证实ADAMTS13功能障碍与多种疾病相关。最近,有报道称ADAMTS13与卒中密切相关。在本综述中,我们简要描述了ADAMTS13的结构及其在血栓形成、炎症以及血管生成中的作用。然后,我们重点关注了ADAMTS13与AIS之间的关系,从缺血性卒中的发生,到AIS的治疗和预后。基于来自基础研究、动物研究和临床研究的结果,我们提出ADAMTS13是指导缺血性卒中合理治疗的潜在生物标志物,也是治疗tPA抵抗性血栓的有前景的治疗药物。