Down-regulation of Cx43 expression on PIH-HUVEC cells attenuates monocyte–endothelial adhesion. Issue 179 (July 2019)

• Record Type: Journal Article
• Authors: Li, Xianlong; Zhang, Qian; Zhang, Rui; Cheng, Nan; Guo, Na; Liu, Yiqian; Cai, Jun; Yuan, Dongdong
• Is Part Of: Thrombosis research. Issue 179(2019)
• Page Start: 104
• Page End: 113
• Publication Date: 2019-07
• Subjects: PIH Pregnancy-induced hypertension -- Cx43 connexin43 -- HUVEC human umbilical vein endothelial cells -- VCAM-1 vascular cell adhesion molecule 1 -- ICAM-1 intercellular adhesion molecule 1 -- GJ Gap junction -- PKA protein kinase A -- PKC protein kinase C -- TNF-α tumor necrosis factor -- HRP horseradish peroxidase; Connexin43 -- Pregnancy-induced hypertension -- monocyte–endothelial adhesion -- PI3K/AKT/NF-κB signaling pathway -- intercellular adhesion molecule 1 -- vascular cell adhesion molecule 1; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2019.05.009
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: 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-κB 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-κB 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-κB signaling pathway activation and VCAM-1 and ICAM-1 over-expression, which ultimately lead to monocyte–endothelial adhesion increase. Highlights: Monocytes adhering on PIH-HUVECs are much more obvious than that on normal HUVECs. Function of Cx43 channels has no effects on cell adhesion. Inhibition of Cx43 protein expression on PIH-HUVECs could attenuate cell adhesion. Cx43 expression affects VCAM-1 and ICAM-1 expression via regulating PI3K/AKT/NF-κB.