Huang Junyang, Ge Shuang, Luo Desha, Du Ruolin, Wang Yang, Liu Wanling, Wang Guixue, Yin Tieying
Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China.
Mater Today Bio. 2022 Aug 27;16:100410. doi: 10.1016/j.mtbio.2022.100410. eCollection 2022 Dec.
As one of the main functions of vascular endothelial cells, Vascular permeability is determined by four tight junction proteins (TJPs): Zonula Occludens-1 (ZO-1), Claudin-5, Occludin and Tricellulin. The barrier function of blood vessels will be reconstructed after they are damaged by endothelial mechanical injuries caused by vascular interventions. In this study, the effects of balloon expansion (transient mechanical injury) on four TJPs and vascular permeability were compared with those of poly--lactic acid bioresorbable scaffolds (BRSs) implantation (continuous mechanical stimulation). We found that BRSs do not affect vascular permeability, while the recovery of vascular barrier function was found to be only related to the mechanical injuries and repair of endothelium. Mechanical stimulation affects and accelerates the recovery process of vascular permeability with the heterogeneous expression levels of TJPs induced after BRSs implantation. Different TJPs have different sensitivity to different loyal mechanical stimuli. ZO-1 is more sensitive to shear stress and tension than to static pressure. Occludin is sensitive to static pressure and shear stress. Tricellulin is more sensitive to tension stretching. Compared with the other three TJPs, Claudin-5 can respond to mechanical stimulation, with relatively low sensitivity, though. This difference in sensitivity determines the heterogeneous expression of TJPs. Mechanical stimulation of different kinds and strengths can also cause different cell morphological changes and inflammatory reactions. As an important element affecting endothelial function, the mechanical factors emerging after BRSs implantation are worthy of more attention.
作为血管内皮细胞的主要功能之一，血管通透性由四种紧密连接蛋白（TJPs）决定：闭合蛋白-1（ZO-1）、紧密连接蛋白-5、闭合蛋白和三联蛋白。血管因血管介入导致的内皮机械损伤而受损后，其屏障功能将得以重建。在本研究中，将球囊扩张（短暂机械损伤）对四种TJPs和血管通透性的影响与聚乳酸生物可吸收支架（BRSs）植入（持续机械刺激）的影响进行了比较。我们发现，BRSs不影响血管通透性，而血管屏障功能的恢复仅与内皮的机械损伤和修复有关。机械刺激通过BRSs植入后诱导的TJPs异质性表达水平来影响并加速血管通透性的恢复过程。不同的TJPs对不同类型的机械刺激具有不同的敏感性。ZO-1对剪切应力和张力比对静压更敏感。闭合蛋白对静压和剪切应力敏感。三联蛋白对拉伸更敏感。与其他三种TJPs相比，紧密连接蛋白-5虽然能对机械刺激做出反应，但其敏感性相对较低。这种敏感性差异决定了TJPs的异质性表达。不同类型和强度的机械刺激也会引起不同的细胞形态变化和炎症反应。作为影响内皮功能的一个重要因素，BRSs植入后出现的机械因素值得更多关注。
