剪切应力对生长在微图案表面内皮细胞骨架排列、黏附、迁移和凋亡的影响

Effects of shear stress on cytoskeleton alignment, adhesion, migration and apoptosis of endothelial cells on micropatterned substrates

背景:微纳米尺寸的表面修饰法为解决心血管植入物材料表面的内皮化问题提供了一个有效方法。剪切应力在心血管植入物内皮化过程中起着重要作用。目的:综述剪切应力对生长在微图案表面上内皮细胞骨架排列、黏附、迁移和凋亡的影响。方法:作者检索2002至2017年Pub Med数据库和中国知网数据库关于剪切应力对生长在微图案表面上内皮细胞影响的文献,英文检索词为"micropattern,flow shear stress,endothelial cells",中文检索词为"微米拓扑结构,微图案,剪切应力,内皮细胞"。结果与结论:对生长在微图案表面的内皮细胞施加平行剪切应力,可促进微丝沿微图案长轴方向排列,促进内皮细胞沿剪切应力方向迁移,上调内皮细胞FAK的磷酸化水平,增强内皮细胞的黏附能力,并改善内皮细胞的活性。有研究认为平行剪切应力促进微管沿微图案长轴方向排列,另有研究认为平行剪切应力对微管排列无影响。有些文献发现垂直剪切应力破坏生长在微图案表面的内皮细胞的微丝和微管结构,减弱微丝和微管沿微图案长轴方向排列的程度,降低内皮细胞的黏附能力和细胞活性;有些文献发现垂直剪切应力未破坏生长在微图案表面内皮细胞骨架的结构与排列,仍能促进内皮细胞沿剪切应力方向的迁移。此外,剪切力大小影响内皮细胞的迁移,随着剪切应力的增大,生长在微图案表面上的内皮细胞沿剪切应力方向迁移的数量增多。

BACKGROUND： Micro-nano-sized modification of the material surface provides an effective way to enhance the endothelialization of cardiovascular implants. Shear stress plays an important role in the endothelialization of cardiovascular implants.OBJECTIVE： To review the effects of flow shear stress on endothelial cell cytoskeleton alignment, migration, adhesion and apoptosis on the micropatterned substrates.METHODS： The author performed a retrieval of PubMed and CNKI databases from 2002 to 2017 to search literatures about the effects of shear stress on endothelial cells on the micropatterned substrates. The keywords were ＂micrometer topology, micropattern, flow shear stress, endothelial cells＂ in English and Chinese, respectively.RESULTS AND CONCLUSION： The shear stress parallel to the long axis of the micropattern which is applied to the endothelial cells on micropatterned substrates promotes endothelial cell microfilaments alignment along the long axis direction of micropattern, strengthens endothelial cell migration along the flow direction, increases the level of FAK phosphorylation, enhances endothelial cell adhesion, and improves endothelial cell activity. However, there are some controversies on the effects of parallel shear stress on the microtubule arrangement of endothelial cells on micropatterned substrates. Some studies have reported that parallel shear stress promotes endothelial cell microtubules alignment along the long axis of micropatterns. But others have found that parallel shear stress has no effect on endothelial cell microtubule arrangement. There are different conclusions about the effects of shear stress perpendicular to the long axis of the micropattern on endothelial cells on the micropatterned substrates. Some literatures have found vertical shear stress destroys the structure of endothelial cell microfilaments and microtubules,weakens the degree of microfilaments and microtubules arranged along the long axis of micropatterns, and attenuates endothelial cell adhesion and cell activity. But some have found vertical shear stress does not destroy the structure and alignment of endothelial cell microfilaments and microtubules, and still can promote endothelial cell migration along the flow direction. The magnitude of shear force affects endothelial cell migration, and the number of endothelial cells on the micropatterned substrates migrating along the flow direction increases with the increasing intensity of shear stress.