Regulation of VWF expression, and secretion in health and disease.
Regulation of VWF expression, and secretion in health and disease.
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DOI：
10.1097/moh.0000000000000230
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发表时间：
2016-05
影响因子：
3.2
通讯作者：
Hwa J
中科院分区：
文献类型：
--
作者：
Xiang Y;Hwa J
VWF是一种大的多结构域、多聚体糖蛋白，在调节凝血和出血之间的平衡中起重要作用。异常VWF调节可导致从出血性疾病（VWD）到异常血栓形成（TTP）的一系列疾病。了解VWF表达和分泌的生物学特性对于开发VWF相关止血疾病的新型靶向疗法至关重要。一些最近优雅的体外和体内研究将突出包括内含子剪接的VWF基因，miRNA调节的VWF基因表达，和syntaxin结合蛋白和自噬介导的VWF分泌的发现。与已经确定的VWF在VWD和TTP病理生理学中的关键作用相比，其他临床研究已经阐明并加强了VWF血浆水平升高与卒中、心肌梗死、静脉血栓形成和糖尿病血栓并发症风险增加的相关性。此外，缺血性中风和心肌梗死的实验小鼠模型进一步支持VWF作为潜在的治疗靶点。VWF的生物合成、成熟和分泌是一个复杂的过程，需要严格的调控。我们对VWF的表达和分泌及其与血栓性疾病的关系的理解取得了重大进展，有助于开发新的靶向VWF药物来预防和治疗止血不足和增强止血。
VWF is a large multi-domain, multimeric glycoprotein that plays an essential role in regulating the balance between blood clotting and bleeding. Aberrant VWF regulation can lead to a spectrum of diseases extending from bleeding disorders (VWD) to aberrant thrombosis (TTP). Understanding the biology of VWF expression and secretion is essential for developing novel targeted therapies for VWF related hemostasis disorders. A number of recent elegant in vitro and in vivo studies will be highlighted including the discovery of intronic splicing in the VWF gene, miRNA regulated VWF gene expression, and syntaxin binding protein and autophagy mediated VWF secretion. Compared with the already established critical role of VWF in VWD and TTP pathophysiology, additional clinical studies have clarified and reinforced the association of increased plasma levels of VWF with an increased risk of stroke, myocardial infarction, venous thrombosis and diabetic thrombotic complications. Moreover, experimental mouse models of ischaemic stroke and myocardial infarction have further support VWF as a potential therapeutic target. VWF biosynthesis, maturation, and secretion is a complex process, which mandates tight regulation. Significant progress has been made in our understandings of VWF expression and secretion and its association with thrombotic diseases, contributing to the development of novel targeting VWF drugs for prevention and treatment of deficient and enhanced hemostasis.