Inverting angiogenesis with interstitial flow and chemokine matrix-binding affinity.
Inverting angiogenesis with interstitial flow and chemokine matrix-binding affinity.
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DOI：
10.1038/s41598-022-08186-0
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发表时间：
2022-03-10
影响因子：
4.6
通讯作者：
Gomez H
中科院分区：
文献类型：
--
作者：
Moure A;Vilanova G;Gomez H
协调血管生成的分子信号通路已被广泛研究，但生物物理线索的作用受到较少关注。间质流在体内是不可避免的，并已被证明可以显着改变新生血管的模式，但流动调节血管生成的机制仍然知之甚少。在这里，我们研究间质流和不同的趋化因子亚型的基质结合的亲和力之间的复杂的相互作用。使用一个计算模型，我们发现，改变基质亲和力的趋化因子亚型可以逆转的影响，间质流血管生成从优先生长的方向上的流动时，趋化因子是最初的矩阵绑定到优先流对流量时，它是未绑定的。虽然流体力信号内皮细胞直接，我们的数据表明，生物运输参数的基础上的反转的机制，并提供了一个潜在的解释实验结果，其中间质流产生的优先血管生长的流动和反对。我们的研究结果指出，在肿瘤微环境中，血管网络的几何形状和间质流动模式是复杂的，间质流动对血管生成的影响特别复杂。
The molecular signaling pathways that orchestrate angiogenesis have been widely studied, but the role of biophysical cues has received less attention. Interstitial flow is unavoidable in vivo, and has been shown to dramatically change the neovascular patterns, but the mechanisms by which flow regulates angiogenesis remain poorly understood. Here, we study the complex interactions between interstitial flow and the affinity for matrix binding of different chemokine isoforms. Using a computational model, we find that changing the matrix affinity of the chemokine isoform can invert the effect of interstitial flow on angiogenesis—from preferential growth in the direction of the flow when the chemokine is initially matrix-bound to preferential flow against the flow when it is unbound. Although fluid forces signal endothelial cells directly, our data suggests a mechanism for the inversion based on biotransport arguments only, and offers a potential explanation for experimental results in which interstitial flow produced preferential vessel growth with and against the flow. Our results point to a particularly intricate effect of interstitial flow on angiogenesis in the tumor microenvironment, where the vessel network geometry and the interstitial flow patterns are complex.
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DOI：
10.1038/nrm3176
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
9.8
作者：
Ghaffari, Siavash;Leask, Richard L.;Jones, Elizabeth A. V.
通讯作者：
Jones, Elizabeth A. V.
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
影响因子：
7.5
作者：
Eilken, Hanna M.;Adams, Ralf H.
通讯作者：
Adams, Ralf H.
DOI：
10.1073/pnas.0503681102
发表时间：
2005-11-01
影响因子：
11.1
作者：
Helm, CLE;Fleury, ME;Swartz, MA
通讯作者：
Swartz, MA