Down-regulation of Cx43 expression on PIH-HUVEC cells attenuates monocyte-endothelial adhesion
Down-regulation of Cx43 expression on PIH-HUVEC cells attenuates monocyte-endothelial adhesion
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PIH-HUVEC 细胞上 Cx43 表达的下调减弱单核细胞与内皮细胞的粘附
DOI：
10.1016/j.thromres.2019.05.009
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发表时间：
2019-07-01
影响因子：
7.5
通讯作者：
Yuan, Dongdong
中科院分区：
文献类型：
--
作者：
Li, Xianlong;Zhang, Qian;Yuan, Dongdong
妊高征（PIH）是妊娠期最常见的严重并发症，可导致显著的母婴发病率和死亡率。血管痉挛是PIH的主要发病机制，引起血流动力学改变和血管内皮细胞损伤。然而，其潜在机制尚不清楚。单核细胞内皮粘附一直被认为是血管内皮细胞损伤的重要指标之一。Connexin43 （Cx43）在单核细胞-内皮细胞粘附中起重要作用。因此，我们探讨了Cx43对pih诱导的血管内皮细胞损伤中细胞粘附的影响。方法：我们从患有或不患有PIH的患者身上获得人脐静脉内皮细胞（HUVECs）。使用不同的方法，如抑制剂：油酰胺和Gap26，或特异性siRNA来改变正常或pih - huvec中的Cx43通道功能或蛋白质表达。检测U937-HUVECs的粘附、粘附分子VCAM-1、ICAM-1的表达以及PI3K/AKT/NF-kappa B信号通路的活性。结果：PIH-HUVECs单核细胞内皮粘附明显高于正常HUVECs。抑制Cx43蛋白表达可显著减弱细胞粘附，而Cx43通道的功能对细胞粘附无影响。通过调节PI3K/AKT/NF-kappa B信号通路活性，改变Cx43蛋白在PIH-HUVECs介导的VCAM-1和ICAM-1表达中的表达。结论：我们首次报道了Cx43蛋白在PIH-HUVECs中的表达明显高于正常HUVECs。血管内Cx43蛋白表达升高导致PI3K/AKT/NF-kappa B信号通路激活，导致VCAM-1和ICAM-1过表达，最终导致单核细胞内皮细胞粘附增加。
Introduction: Pregnancy-induced hypertension (PIH) is the most common serious complication of pregnancy, resulting in significant maternal and fetal morbidity and mortality. Vasospasm is the main pathogenesis of PIH, which leads to the hemodynamic changes and the injury of vascular endothelial cells. However, the underlying mechanism is still unclear. Monocyte-endothelial adhesion is always considered to be one of the most important indicators of vascular endothelial cell injury. Connexin43 (Cx43) plays an important part in monocyte- endothelial adhesion. Thus, we explored effects of Cx43 on cell adhesion in PIH-induced vascular endothelial cells injury.Methods: We obtained human umbilical vein endothelial cells (HUVECs) from patients with or without PIH. Different methods, such as inhibitors: oleamide and Gap26, or specific siRNA were used to alter Cx43 channels function or protein expression in normal or PIH-HUVECs. U937-HUVECs adhesion, adhesion molecules expression, such as VCAM-1 and ICAM-1, and the activity of PI3K/AKT/NF-kappa B signaling pathway were determined.Results: Monocyte-endothelial adhesion on PIH-HUVECs was much more obvious than that on normal HUVECs. Inhibition of Cx43 protein expression could attenuate cell adhesion significantly, however, function of Cx43 channels had no effects on it. Alternation of Cx43 protein expression on PIH-HUVECs mediated VCAM-1 and ICAM-1 expression via regulating the activity of PI3K/AKT/NF-kappa B signaling pathway.Conclusions: We firstly reported Cx43 protein expression on PIH-HUVECs was much higher than that on normal HUVECs. Elevation of Cx43 protein expression within the vasculature resulted in PI3K/AKT/NF-kappa B signaling pathway activation and VCAM-1 and ICAM-1 over-expression, which ultimately lead to monocyte-endothelial adhesion increase.