Blood flow governs transport of oxygen and nutrients into tissues. Hypoxic tissues secrete VEGFs to promote angiogenesis during development and in tissue homeostasis. In contrast, tumors enhance pathologic angiogenesis during growth and metastasis, suggesting suppression of tumor angiogenesis could limit tumor growth. In line with these observations, various factors have been identified to control vessel formation in the last decades. However, their impact on the vascular transport properties of oxygen remain elusive. Here, we take a computational approach to examine the effects of vascular branching on blood flow in the growing vasculature. First of all, we reconstruct the 3D vascular model from the 2D confocal images of the growing vasculature at P6 mouse retina, then simulate blood flow in the vasculature, which is applied for the gene targeting mouse models causing hypo- or hyper-branching vascular formation. Interestingly, hyper-branching morphology attenuates effective blood flow at the angiogenic front and promotes tissue hypoxia. In contrast, vascular hypo-branching enhances blood supply at the angiogenic front of the growing vasculature. Oxygen supply by newly formed blood vessels improves local hypoxia and decreases VEGF expression at the angiogenic front during angiogenesis. Consistent with the simulation results indicating improved blood flow in the hypo-branching vasculature, VEGF expression around the angiogenic front is reduced in those mouse retinas. Conversely, VEGF expression was enhanced in the hyper-branching vasculature in the mouse retina. Our results indicate the importance of detailed flow analysis in evaluating the vascular transport properties of branching morphology of the blood vessels.

中文翻译：

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数值评估揭示了分支形态对血管生成过程中血管运输特性的影响

血流控制着氧气和营养物质向组织的运输。缺氧组织分泌VEGF，以促进发育过程中和组织稳态中的血管生成。相反，肿瘤在生长和转移过程中会增强病理性血管生成，提示抑制肿瘤血管生成可能会限制肿瘤的生长。根据这些观察结果，在过去的几十年中已经确定了各种因素来控制血管的形成。然而，它们对氧气的血管运输特性的影响仍然难以捉摸。在这里，我们采用一种计算方法来检查血管分支对不断增长的脉管系统中血流的影响。首先，我们从P6小鼠视网膜上不断增长的脉管系统的2D共聚焦图像重建3D血管模型，然后模拟脉管系统中的血流，应用于靶向小鼠模型的基因，该基因会引起分支血管过度分支或过度分支。有趣的是，超支化形态会削弱血管生成前沿的有效血流量并促进组织缺氧。相反，血管分支不足会增加正在生长的脉管系统的血管生成前端的血液供应。通过新生血管的氧气供应改善了局部缺氧并降低了血管生成过程中血管生成前沿的VEGF表达。与模拟结果一致，表明分支支配的脉管系统中的血流得到改善，在那些小鼠视网膜中，血管生成前沿周围的VEGF表达降低。相反，在小鼠视网膜的超支脉管系统中，VEGF表达增强。