Extracellular matrix density regulates the rate of neovessel growth and branching in sprouting angiogenesis.
Extracellular matrix density regulates the rate of neovessel growth and branching in sprouting angiogenesis.
复制标题
细胞外基质密度调节新血管生长和萌芽血管生成中的分支速率。
DOI：
10.1371/journal.pone.0085178
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Weiss JA
中科院分区：
文献类型：
--
作者：
Edgar LT;Underwood CJ;Guilkey JE;Hoying JB;Weiss JA
血管生成受局部微环境的调控，包括新生血管芽和细胞外基质（ECM）之间的机械相互作用。然而，在发芽血管生成过程中，ECM的力学和生物物理特性与新血管生长的关系的控制机制才刚刚开始被理解。在这项研究中，我们表征了基质密度和微血管拓扑结构之间的关系，在体外三维器官培养模型的发芽血管生成。我们使用这些结果来设计和校准一个计算生长模型，以证明单个新血管行为的变化如何产生实验观察到的血管拓扑结构的变化。具有较高胶原密度的血管化凝胶产生的新血管具有更短的血管长度，更少的分支点和更低的网络互联性。该计算模型能够通过根据局部基质密度缩放新血管生长和分支的速率来预测这些实验结果。作为建模框架效用的最后演示，我们使用我们的生长模型来预测几种实际情况，这些情况无法使用器官培养模型进行实验研究。在血管生成的三维器官培养模型中，增加ECM的密度显著减少血管生成和网络形成。增加基质的密度增加了ECM的刚度，改变了新血管变形和重塑周围环境的方式。本研究中概述的计算框架能够通过根据局部ECM密度调整新血管生长速率和分支概率来预测观察到的实验行为，这表明通过增加基质密度来改变ECM的刚度会影响新血管的行为，从而调节血管生成过程中的血管拓扑结构。
Angiogenesis is regulated by the local microenvironment, including the mechanical interactions between neovessel sprouts and the extracellular matrix (ECM). However, the mechanisms controlling the relationship of mechanical and biophysical properties of the ECM to neovessel growth during sprouting angiogenesis are just beginning to be understood. In this research, we characterized the relationship between matrix density and microvascular topology in an in vitro 3D organ culture model of sprouting angiogenesis. We used these results to design and calibrate a computational growth model to demonstrate how changes in individual neovessel behavior produce the changes in vascular topology that were observed experimentally. Vascularized gels with higher collagen densities produced neovasculatures with shorter vessel lengths, less branch points, and reduced network interconnectivity. The computational model was able to predict these experimental results by scaling the rates of neovessel growth and branching according to local matrix density. As a final demonstration of utility of the modeling framework, we used our growth model to predict several scenarios of practical interest that could not be investigated experimentally using the organ culture model. Increasing the density of the ECM significantly reduced angiogenesis and network formation within a 3D organ culture model of angiogenesis. Increasing the density of the matrix increases the stiffness of the ECM, changing how neovessels are able to deform and remodel their surroundings. The computational framework outlined in this study was capable of predicting this observed experimental behavior by adjusting neovessel growth rate and branching probability according to local ECM density, demonstrating that altering the stiffness of the ECM via increasing matrix density affects neovessel behavior, thereby regulated vascular topology during angiogenesis.
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影响因子：
2.7
作者：
FISHER, C;GILBERTSONBEADLING, S;MITCHELL, MA
通讯作者：
MITCHELL, MA
DOI：
10.1073/pnas.76.1.514
发表时间：
1979-01-01
影响因子：
11.1
作者：
BOTTENSTEIN, JE;SATO, GH
通讯作者：
SATO, GH
影响因子：
4.1
作者：
Kniazeva, Ekaterina;Kachgal, Suraj;Putnam, Andrew J.
通讯作者：
Putnam, Andrew J.
影响因子：
3.4
作者：
Guo, WH;Frey, MT;Wang, YL
通讯作者：
Wang, YL
影响因子：
2.8
作者：
Califano, Joseph P.;Reinhart-King, Cynthia A.
通讯作者：
Reinhart-King, Cynthia A.