scholarly journals Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43/PKC-α/NOX2/ROS Signaling Pathway in Monocytes

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yunfei Chai ◽  
Zhongming Cao ◽  
Runying Yu ◽  
Yong Liu ◽  
Dongdong Yuan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Cx43 Expression ◽  
Ros Signaling ◽  
Pathway Activation ◽  
Carboxyl Terminal ◽  
Umbilical Vein Endothelial Cells ◽  
Inflammation Reaction

Dexmedetomidine is widely used for sedating patients in operation rooms or intensive care units. Its protective functions against oxidative stress, inflammation reaction, and apoptosis have been widely reported. In present study, we explored the effects of dexmedetomidine on monocyte-endothelial adherence. We built lipopolysaccharide- (LPS-) induced monocyte-endothelial adherence models with U937 monocytes and human umbilical vein endothelial cells (HUVECs) and observed the effects of dexmedetomidine on U937-HUVEC adhesion. Specific siRNA was designed to knock-down Connexin43 (Cx43) expression in U937 monocytes. Gö6976, GSK2795039, and NAC were used to inhibit PKC-α, NOX2, and ROS, respectively. Then, we detected whether dexmedetomidine could downregulate Cx43 expression and its downstream PKC-α/NOX2/ROS signaling pathway activation and ultimately result in the decrease of U937-HUVEC adhesion. The results showed that dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), could inhibit adhesion of molecule expression (VLA-4 and LFA-1) and U937-HUVEC adhesion. Simultaneously, it also attenuated Cx43 expression in U937 monocytes. With the downregulation of Cx43 expression, the activity of PKC-α and its related NOX2/ROS signaling pathway were reduced. Inhibiting PKC-α/NOX2/ROS signaling pathway with Gö6976, GSK2795039, and NAC, respectively, VLA-4, LFA-1 expression, and U937-HUVEC adhesion were all decreased. In summary, we concluded that dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), decreased Cx43 expression in U937 monocytes and PKC-α associated with carboxyl-terminal domain of Cx43 protein. With the downregulation of PKC-α, the NOX2/ROS signaling pathway was inhibited, resulting in the decrease of VLA-4 and LFA-1 expression. Ultimately, U937-HUVEC adhesion was reduced.

scholarly journals VGLL4 Protects against Oxidized-LDL-Induced Endothelial Cell Dysfunction and Inflammation by Activating Hippo-YAP/TEAD1 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Kaicheng Xu ◽  
Haomin Zhao ◽  
Xiaolei Qiu ◽  
Xiwen Liu ◽  
Fucheng Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Oxidized Ldl ◽  
Endothelial Cell Dysfunction ◽  
Human Umbilical Vein ◽  
Cell Dysfunction ◽  
Umbilical Vein Endothelial Cells

Vestigial-like 4 (VGLL4) has been found to have multiple functions in tumor development; however, its role in cardiovascular disease is unknown. The aim of this study was to investigate the effect of VGLL4 on the dysfunction and inflammatory response of Ox-LDL-induced human umbilical vein endothelial cells (HUVECs) and its mechanism, so as to provide a new theoretical basis for the diagnosis and treatment of atherosclerosis. In the present study, the protective activity of VGLL4 inhibiting Ox-LDL-induced apoptosis, oxidative stress, inflammation, and injury as well as its molecular mechanisms was examined using human umbilical vein endothelial cells (HUVECs). The results showed that the expression of VGLL4 was decreased with the increase of Ox-LDL concentration in HUVECs. In addition, the functional study found that VGLL4 overexpression alleviated Ox-LDL-induced oxidative stress, inflammation, and dysfunction and inhibited apoptosis. Further research found that VGLL4 regulated Hippo-YAP/TEAD1 signaling pathway, and the Hippo-YAP/TEAD1 signaling pathway was involved in the protective mechanism of VGLL4 on HUVECs. In conclusion, it suggests that VGLL4 protects against oxidized-LDL-induced endothelial cell dysfunction by activating the Hippo-YAP/TEAD1 signaling pathway.

scholarly journals Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 558-569
Author(s):  
Qiuxia Su ◽  
Xianhua Dong ◽  
Chonghui Tang ◽  
Xiaojie Wei ◽  
Youguo Hao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Luciferase Reporter ◽  
Low Density ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Abstract Atherosclerosis (AS) is a serious cardiovascular disease. Circular RNAs (circRNAs) play an important role in the progression of many diseases, including AS. However, the role of circ_0003204 in AS is not clear. Oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) were used to construct an AS cell model in vitro. Cell viability was assessed using cell counting kit 8 (CCK8) assay. Flow cytometry and caspase-3 activity were used to measure cell apoptosis. The contents of inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Oxidative stress marker expression and cell injury marker activity were detected by their corresponding Assay Kits. Besides, the expression levels of circ_0003204, miR-330-5p, and toll-like receptor 4 (TLR4) were tested by real-time polymerase chain reaction (qPCR). The interaction between miR-330-5p and circ_0003204 or TLR4 was examined by dual-luciferase reporter assay and RNA pull-down assay. Western blot (WB) analysis was used to determine the levels of TLR4 protein and nuclear factor-kappa B (NF-κB) signaling pathway-related protein. Our data suggested that ox-LDL could suppress viability and promote apoptosis, inflammatory response, and oxidative stress in HUVECs. circ_0003204 was highly expressed in ox-LDL-induced HUVECs, and its silencing could inhibit ox-LDL-induced HUVECs injury. miR-330-5p could be sponged by circ_0003204, and its inhibitor could reverse the inhibition effect of silenced circ_0003204 on ox-LDL-induced HUVECs injury. Further, TLR4 could be targeted by miR-330-5p, and its overexpression could invert the suppression effect of miR-330-5p on ox-LDL-induced HUVECs injury. The activity of the NF-κB signaling pathway was regulated by the circ_0003204/miR-330-5p/TLR4 axis. Our results indicated that circ_0003204 silencing could alleviate ox-LDL-induced HUVECs injury, suggesting that circ_0003204 might be a novel target for AS treatment.

scholarly journals Cytoprotective Role of Edible Seahorse (Hippocampus abdominalis)-Derived Peptides in H2O2-Induced Oxidative Stress in Human Umbilical Vein Endothelial Cells

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 86
Author(s):  
Yunok Oh ◽  
Chang-Bum Ahn ◽  
Jae-Young Je
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Combination Treatment ◽  
Umbilical Vein ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Staining ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Oxidative stress-induced endothelial dysfunction is strongly linked to the pathogenesis of cardiovascular diseases. A previous study revealed that seahorse hydrolysates ameliorated oxidative stress-mediated human umbilical vein endothelial cells (HUVECs) injury. However, the responsible compounds have not yet been identified. This study aimed to identify cytoprotective peptides and to investigate the molecular mechanism underlying the cytoprotective role in H2O2-induced HUVECs injury. After purification by gel filtration and HPLC, two peptides were sequenced by liquid chromatography-tandem mass spectrometry as HGSH (436.43 Da) and KGPSW (573.65 Da). The synthesized peptides and their combination (1:1 ratio) showed significant HUVECs protection effect at 100 μg/mL against H2O2-induced oxidative damage via significantly reducing intracellular reactive oxygen species (ROS). Two peptides and their combination treatment resulted in the increased heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, through the activation of nuclear transcription factor-erythroid 2-related factor (Nrf2). Additionally, cell cycle and nuclear staining analysis revealed that two peptides and their combination significantly protected H2O2-induced cell death through antiapoptotic action. Two peptides and their combination treatment led to inhibit the expression of proapoptotic Bax, the release of cytochrome C into the cytosol, the activation of caspase 3 by H2O2 treatment in HUVECs, whereas antiapoptotic Bcl-2 expression was increased with concomitant downregulation of Bax/Bcl-2 ratio. Taken together, these results suggest that seahorse-derived peptides may be a promising agent for oxidative stress-related cardiovascular diseases.

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