• Ye-Yu Zhao, Shao-Xin Huang, Zheng Hao, Hua-Xin Zhu, Ze-Long Xing, and Mei-Hua Li.
• Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, Nanchang, China.
• World Neurosurg. 2020 Apr 1; 136: e469-e475.

ObjectiveThe present study aimed to characterize the mechanism of fluid shear stress (FSS)-induced endothelial cell (EC) injury via protein kinase C alpha (PKCα)-mediated vascular endothelial cadherin (VE-cadherin) and p120-catenin (p120ctn) expression.MethodsWe designed a T chamber system that produced stable FSS on ECs in vitro. Human umbilical vein endothelial cells (HUVECs) in which PKCα was knocked down and normal HUVECs were cultured on the coverslips. FSS was impinged on these 2 types of ECs for 0 hours and 6 hours. The morphology and density of HUVECs were evaluated, and expression levels of phosphorylated PKCα, p120-catenin (p120ctn), VE-cadherin, phosphorylated p120ctn at S879 (p-S879p120ctn), and nuclear factor kappa B (NF-κB) were analyzed by Western blot.ResultsHUVECs exposed to FSS were characterized by a polygonal shape and decreased cell density. The phosphorylated PKCα level was increased under FSS at 6 hours (P < 0.05). In normal HUVECs during FSS, p120ctn and VE-cadherin were decreased, whereas p-S879p120ctn and NF-κB were increased, at 6 hours (P < 0.05). In HUVECs after PKCα knockdown, p120ctn and VE-cadherin were not significantly changed (P > 0.05), p-S879p120ctn was undetectable, but NF-κB was decreased (P < 0.05) at 6 hours.ConclusionsThe possible mechanism of FSS-induced EC injury may be as follows: 1) PKCα induces low expression of p120ctn, which leads to activation of NF-κB and degradation of VE-cadherin; 2) PKCα-mediated phosphorylation of p120ctn at S879 disrupts p120ctn binding to VE-cadherin.Copyright © 2020 Elsevier Inc. All rights reserved.

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