Flow dynamics control the location of sprouting and direct elongation during developmental angiogenesis
Flow dynamics control the location of sprouting and direct elongation during developmental angiogenesis
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DOI：
10.1242/dev.128058
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发表时间：
2015-12-01
期刊：
影响因子：
4.6
通讯作者：
Jones, Elizabeth A. V.
中科院分区：
文献类型：
--
作者：
Ghaffari, Siavash;Leask, Richard L.;Jones, Elizabeth A. V.
血管生成受到许多信号通路的严格控制。尽管我们对血管生成所涉及的分子机制的了解迅速增加，但生物力学信号在此过程中发挥的作用尚未得到充分研究。我们最近开发了一种技术，通过延时显微镜同时分析禽类胚胎毛细血管丛中的流动动力学和血管重塑，并用它来研究血管生成萌芽期间存在的血流动力学环境。我们发现，芽总是从压力较低的容器向压力较高的容器形成，并且芽在剪切应力最小的位置形成，但要避免两个血流合并的位置，即使该点的剪切应力水平比芽位置低。使用这些参数，我们能够成功预测鹌鹑胚胎中的发芽位置。我们还发现，两个容器之间的压力差允许伸长，如果压力差变为负值，芽会改变方向或倒退。此外，芽伸长率与两个容器之间的压力差成正比。我们的结果表明，流动动力学可以预测灌注血管网络中芽形成的位置，并且间质上的压力差可以引导芽伸长。
Angiogenesis is tightly controlled by a number of signalling pathways. Although our understanding of the molecular mechanisms involved in angiogenesis has rapidly increased, the role that biomechanical signals play in this process is understudied. We recently developed a technique to simultaneously analyse flow dynamics and vascular remodelling by time-lapse microscopy in the capillary plexus of avian embryos and used this to study the hemodynamic environment present during angiogenic sprouting. We found that sprouts always form from a vessel at lower pressure towards a vessel at higher pressure, and that sprouts form at the location of a shear stress minimum, but avoid locations where two blood streams merge even if this point is at a lower level of shear stress than the sprouting location. Using these parameters, we were able to successfully predict sprout location in quail embryos. We also found that the pressure difference between two vessels is permissive to elongation, and that sprouts will either change direction or regress if the pressure difference becomes negative. Furthermore, the sprout elongation rate is proportional to the pressure difference between the two vessels. Our results show that flow dynamics are predictive of the location of sprout formation in perfused vascular networks and that pressure differences across the interstitium can guide sprout elongation.