Fluid shear stress combined with shear stress spatial gradients regulates vascular endothelial morphology,Integrative Biology

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Fluid shear stress combined with shear stress spatial gradients regulates vascular endothelial morphology
Integrative Biology ( IF 1.5 ) Pub Date : 2017-05-26 , DOI: 10.1039/c7ib00065k
Daisuke Yoshino _{1,

2,

3,

4,

5} , Naoya Sakamoto _{4,

6,

7,

8} , Masaaki Sato _{2,

4,

5,

9}

Affiliation

High shear stress (SS) causes local changes around arterial bifurcations, which are common sites for cerebral aneurysms. High SS and SS spatial gradient (SSG) are thought to play important roles in the pathology of cerebral aneurysms. However, whether SS and SSG independently affect the function and morphology of vascular endothelial cells (ECs) exposed to fluid flow remains unclear. This study evaluated the morphology of ECs exposed to various SS and SSG combinations. Confluent ECs were exposed to a SS of 2–60 Pa and a uniform SSG of 0, 5, 10, or 15 Pa mm⁻¹ for 24 h. Although ECs exposed to lower levels of SS/SSG were not oriented or elongated in the direction of flow, they began to exhibit orientation, elongation, and development of actin stress fibers under the conditions of SS with a SSG when the SS exceeded a threshold value depending on the magnitude of SSG. Using a simplified computational model, we found that the presence of a SSG affects the strain field in ECs, resulting in a morphological response. SS combined with a SSG can alter the localization of SS mechano-sensing proteins along the strain field as a result of shear flow. Our results suggest that the magnitude of the relationship between SS and SSG plays an important role in regulating morphological changes in ECs in response to fluid flow by regulating EC polarity.

中文翻译：

流体剪切应力与剪切应力空间梯度相结合调节血管内皮形态

高剪切应力（SS）引起动脉分叉周围的局部变化，这是脑动脉瘤的常见部位。高SS和SS空间梯度（SSG）被认为在脑动脉瘤的病理中起重要作用。然而，SS和SSG是否独立影响暴露于流体流的血管内皮细胞（EC）的功能和形态尚不清楚。这项研究评估了暴露于各种SS和SSG组合的EC的形态。汇合的EC暴露于2-60 Pa的SS和0、5、10或15 Pa mm ^-1的均匀SSG持续24小时。尽管暴露于较低SS / SSG水平的EC并未在流动方向上取向或拉长，但当SS超过阈值时，在具有SSG的SS条件下，它们开始表现出肌动蛋白应力纤维的取向，伸长和发育取决于SSG的大小。使用简化的计算模型，我们发现SSG的存在会影响EC中的应变场，从而导致形态响应。SS与SSG结合可以通过剪切流改变SS机械感测蛋白沿应变场的定位。我们的结果表明，SS和SSG之间关系的大小在通过调节EC极性调节流体响应流体的EC形态变化中起着重要作用。

更新日期：2017-05-26

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