Department of Thoracic Surgery, Affiliated Hospital of Beihua University, Jilin 132013, China.
Department of Second Cardiovascular, Qianguo County Hospital, Songyuan 138000, China.
Heart Surg Forum. 2021 Aug 26;24(4):E764-E768. doi: 10.1532/hsf.3405.
Hypoxia induced injury of pulmonary microvascular endothelial barrier is closely related to the pathogenesis of acute lung injury after lung transplantation. VE-cadherin is an important structural molecule for pulmonary microvascular endothelial barrier. In this study, we aim to investigate the roles of VE-cadherin in hypoxia induced injury of pulmonary microvascular endothelial barrier.
Rat model of hypoxia and cultured pulmonary microvascular endothelial cells (PMVECs) were utilized. Determination of PMVECs apoptosis, skeleton combination was conducted to verify the effects of hypoxia on injury of pulmonary microvascular endothelial barrier. In addition, VE-cadherin expression was modulated by administration of siRNA in order to investigate the roles of VE-cadherin in hypoxia induced PMVECs apoptosis and skeleton recombination.
Our data indicated that expression of VE-cadherin was down-regulated in hypoxia-exposed PMVECs. Whereas, in the cells treated using siRNA, down-regulation of VE-cadherin did not trigger PMVECs apoptosis, but it increased the sensitivity of PMVECs to the hypoxia induced apoptosis. In cases of hypoxia, the expression of VE-cadherin was significantly down-regulated, together with endothelial skeleton recombination and increase of permeability, which then triggered endothelial barrier dysfunction.
These data verify that VE-cadherin expression played an important role in hypoxia induced PMVECs apoptosis and cellular skeletal recombination.
肺微血管内皮屏障缺氧损伤与肺移植后急性肺损伤的发病机制密切相关。VE-钙黏蛋白是肺微血管内皮屏障的重要结构分子。本研究旨在探讨 VE-钙黏蛋白在缺氧诱导的肺微血管内皮屏障损伤中的作用。
利用大鼠缺氧模型和培养的肺微血管内皮细胞（PMVECs），测定 PMVECs 凋亡、骨架组合，验证缺氧对肺微血管内皮屏障损伤的影响。此外，通过 siRNA 调节 VE-钙黏蛋白的表达，以探讨 VE-钙黏蛋白在缺氧诱导的 PMVECs 凋亡和骨架重组中的作用。
我们的数据表明，缺氧暴露的 PMVECs 中 VE-钙黏蛋白表达下调。然而，在用 siRNA 处理的细胞中，VE-钙黏蛋白的下调并没有引发 PMVECs 凋亡，反而增加了 PMVECs 对缺氧诱导凋亡的敏感性。在缺氧情况下，VE-钙黏蛋白的表达明显下调，同时内皮骨架重组和通透性增加，导致内皮屏障功能障碍。
这些数据证实，VE-钙黏蛋白表达在缺氧诱导的 PMVECs 凋亡和细胞骨架重组中发挥重要作用。
