Sprouting angiogenesis is an essential vascularisation mechanism consisting of sprouting and remodelling. The remodelling phase is driven by rearrangements of endothelial cells (ECs) within the post-sprouting vascular plexus. Prior work has uncovered how ECs polarise and migrate in response to flow-induced wall shear stress (WSS). However, the question of how the presence of erythrocytes (well-known as RBCs) and their haemodynamics impact affects vascular remodelling remains unanswered. Here, we devise a computational framework to model cellular blood flow in developmental mouse retina. We demonstrate a previously unreported highly heterogeneous distribution of RBCs in primitive vasculature. Furthermore, we report a strong association between vessel regression and RBC depletion, and identify plasma skimming as the driving mechanism. Live imaging in a developmental zebrafish model confirms this association. Taken together, our results indicate that RBC dynamics are fundamental to establishing the regional WSS differences driving vascular remodelling via their ability to modulate effective viscosity.

中文翻译：

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发育性血管网络中红细胞动力学与血管重塑之间的关联

发芽的血管生成是由发芽和重塑组成的基本血管形成机制。重塑阶段是由发芽后血管丛内的内皮细胞（EC）重排驱动的。先前的工作揭示了EC如何响应流动引起的壁剪切应力（WSS）极化和迁移。然而，关于红细胞（众所周知的红细胞）的存在及其血流动力学影响如何影响血管重塑的问题仍未得到解答。在这里，我们设计了一个计算框架来模拟发育中的小鼠视网膜中的细胞血流。我们展示了原始脉管系统中以前未报道的RBCs的高度异质分布。此外，我们报告了血管退化与RBC耗竭之间有很强的联系，并确定撇脂是驱动机制。斑马鱼发育模型中的实时成像证实了这种关联。两者合计，我们的结果表明RBC动力学是建立区域WSS差异的基础，这些差异通过调节有效粘度的能力来驱动血管重塑。