Baksamawi Hosam Alden, Alexiadis Alessio, Vigolo Daniele, Brill Alexander
School of Chemical Engineering, University of Birmingham, Birmingham, United Kingdom.
School of Biomedical Engineering, The University of Sydney, Sydney, NSW, Australia.
Front Cardiovasc Med. 2023 Apr 27;10:1167884. doi: 10.3389/fcvm.2023.1167884. eCollection 2023.
Deep vein thrombosis is a life-threatening disease that takes millions of people's lives worldwide. Given both technical and ethical issues of using animals in research, it is necessary to develop an appropriate model that would recapitulate the conditions of venous thrombus development. We present here a novel microfluidics vein-on-a-chip with moving valve leaflets to mimic the hydrodynamics in a vein, and Human Umbilical Vein Endothelial Cell (HUVEC) monolayer. A pulsatile flow pattern, typical for veins, was used in the experiments. Unstimulated human platelets, reconstituted with the whole blood, accumulated at the luminal side of the leaflet tips proportionally to the leaflet flexibility. Platelet activation by thrombin induced robust platelet accrual at the leaflet tips. Inhibition of glycoprotein (GP) IIb-IIIa did not decrease but, paradoxically, slightly increased platelet accumulation. In contrast, blockade of the interaction between platelet GPIb and A1 domain of von Willebrand factor completely abolished platelet deposition. Stimulation of the endothelium with histamine, a known secretagogue of Weibel-Palade bodies, promoted platelet accrual at the basal side of the leaflets, where human thrombi are usually observed. Thus, platelet deposition depends on the leaflet flexibility, and accumulation of activated platelets at the valve leaflets is mediated by GPIb-VWF interaction.
深静脉血栓形成是一种危及生命的疾病，在全球范围内夺走了数百万人的生命。鉴于在研究中使用动物存在技术和伦理问题，有必要开发一种合适的模型来概括静脉血栓形成的条件。我们在此展示了一种新型的微流控静脉芯片，其具有可移动的瓣膜小叶以模拟静脉中的流体动力学，以及人脐静脉内皮细胞（HUVEC）单层。实验中使用了静脉典型的脉动流模式。用全血重构的未刺激的人血小板，根据小叶的柔韧性，在小叶尖端的管腔侧成比例地积累。凝血酶诱导的血小板活化导致小叶尖端大量血小板聚集。糖蛋白（GP）IIb-IIIa的抑制并没有减少，反而反常地略微增加了血小板的积累。相反，血小板糖蛋白Ib与血管性血友病因子A1结构域之间相互作用的阻断完全消除了血小板的沉积。用组胺刺激内皮细胞（一种已知的魏尔-帕拉德小体促分泌剂），促进了小叶基底侧的血小板聚集，而人类血栓通常在此处形成。因此，血小板沉积取决于小叶的柔韧性，并且活化血小板在瓣膜小叶处的积累是由糖蛋白Ib-血管性血友病因子相互作用介导的。
