Choi Seon Jae, Lillicrap David
Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
J Thromb Haemost. 2020 Apr;18(4):781-785. doi: 10.1111/jth.14743. Epub 2020 Feb 26.
Von Willebrand factor (VWF) is a critical component of the hemostatic system. Basal secretion of VWF from endothelial cells is the principal determinant of an individual's baseline plasma VWF levels, while endothelial VWF release can also be induced by several biochemical agonists and biomechanical forces such as increased shear stress. However, the mechanotransduction machinery responsible for this latter response is unclear. Here we propose that the endothelial glycocalyx (EGC), a dynamic layer of proteins and carbohydrates that covers the surface of the vascular endothelium, may play a key role in mediating this response. The EGC has previously been implicated in mediating the mechanotransduction of shear stress in other shear-responsive endothelial processes, such as nitric oxide production and stem cell differentiation. Here, we hypothesize that a similar mechanism may be responsible for the basal secretion of endothelial VWF, whereby the EGC mediates the mechanotransduction of physiological shear stress generated by flowing blood, that in turn contributes to the maintenance of physiological plasma VWF levels.
血管性血友病因子(VWF)是止血系统的关键组成部分。内皮细胞VWF的基础分泌是个体血浆VWF基线水平的主要决定因素,而内皮VWF的释放也可由多种生化激动剂和生物力学力诱导,如剪切应力增加。然而,负责后一种反应的机械转导机制尚不清楚。在此,我们提出内皮糖萼(EGC),一层覆盖血管内皮表面的动态蛋白质和碳水化合物层,可能在介导这种反应中起关键作用。EGC先前已被证明在其他剪切力响应性内皮过程中,如一氧化氮生成和干细胞分化,介导剪切应力的机械转导。在此,我们假设类似的机制可能负责内皮VWF的基础分泌,即EGC介导流动血液产生的生理剪切应力的机械转导,进而有助于维持生理血浆VWF水平。