Agonist-mediated exocytosis of Weibel-Palade bodies underpins the endothelium’s ability to respond to injury or infection. Much of this important response is mediated by the major constituent of Weibel-Palade bodies: the ultra-large glycoprotein von Willebrand factor. Upon regulated WPB exocytosis, von Willebrand factor multimers unfurl into long, platelet-catching ‘strings’ which instigate the pro-haemostatic response. Accordingly, excessive levels of VWF are associated with thrombotic pathologies, including myocardial infarction and ischaemic stroke.

Failure to appropriately cleave von Willebrand Factor strings results in thrombotic thrombocytopenic purpura, a life-threatening pathology characterised by tissue ischaemia and multiple microvascular occlusions. Historically, treatment of thrombotic thrombocytopenic purpura has relied heavily on plasma exchange therapy. However, the demonstrated efficacy of Rituximab and Caplacizumab in the treatment of acquired thrombotic thrombocytopenic purpura highlights how insights into pathophysiology can improve treatment options for von Willebrand factor-related disease. Directly limiting von Willebrand factor release from Weibel-Palade bodies has the potential as a therapeutic for cardiovascular disease. Cell biologists aim to map the WPB biogenesis and secretory pathways in order to find novel ways to control von Willebrand factor release. Emerging paradigms include the modulation of Weibel-Palade body size, trafficking and mechanism of fusion. This review focuses on the promise, progress and challenges of targeting Weibel-Palade bodies as a means to inhibit von Willebrand factor release from endothelial cells.

激动剂介导的 Weibel-Palade 体胞吐作用支持内皮细胞对损伤或感染作出反应的能力。这种重要的反应大部分是由 Weibel-Palade 小体的主要成分介导的：超大糖蛋白 von Willebrand 因子。在调节 WPB 胞吐作用后，von Willebrand 因子多聚体展开成长的、捕获血小板的“字符串”，从而引发促止血反应。因此，过量水平的 VWF 与血栓形成病理有关，包括心肌梗塞和缺血性中风。

未能正确切割 von Willebrand 因子串会导致血栓性血小板减少性紫癜，这是一种以组织缺血和多处微血管闭塞为特征的危及生命的病理。历史上，血栓性血小板减少性紫癜的治疗严重依赖血浆置换疗法。然而，利妥昔单抗和 Caplacizumab 在治疗获得性血栓性血小板减少性紫癜方面的已证实疗效突出了对病理生理学的深入了解如何改善血管性血友病因子相关疾病的治疗选择。直接限制 Weibel-Palade 小体释放的 von Willebrand 因子具有治疗心血管疾病的潜力。细胞生物学家旨在绘制 WPB 生物发生和分泌途径，以找到控制 von Willebrand 因子释放的新方法。新兴范式包括调节 Weibel-Palade 身体大小、运输和融合机制。本综述重点关注靶向 Weibel-Palade 小体作为抑制血管内皮细胞释放血管性血友病因子的手段的前景、进展和挑战。