scholarly journals Evodiamine Attenuates P2X7-Mediated Inflammatory Injury of Human Umbilical Vein Endothelial Cells Exposed to High Free Fatty Acids

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yun Xue ◽  
Ting Guo ◽  
Lifang Zou ◽  
Yingxin Gong ◽  
Bing Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Endothelial Cells ◽  
Free Fatty Acids ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Human Umbilical Vein ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Umbilical Vein Endothelial Cells

Insulin resistance and type 2 diabetes mellitus (T2DM) are highly prevalent around the world. Elevated concentrations of free fatty acids (FFAs) are closely related to insulin resistance and T2DM. P2X7 receptor is an ion channel gated by ATP, which is implicated in various scenarios including immune response, pain, and inflammation. In this study, we have explored whether P2X7 receptor is involved in pathological changes in human umbilical vein endothelial cells (HUVECs) induced by high FFA treatment, and the potential beneficial effects of evodiamine. Evodiamine could effectively suppress the enhanced expression of P2X7 receptor caused by high FFAs at both mRNA and protein levels. In addition, high FFA-induced cytotoxicity, the upregulated release of ATP, and production of reactive oxygen species (ROS) could be ameliorated by evodiamine in HUVECs. Evodiamine could also reverse the decreased NO formation and the increased adhesive events of immune cells at high FFAs. Moreover, evodiamine inhibited P2X7-dependent TNF-α expression and ERK 1/2 phosphorylation due to high FFAs. All these results indicated that evodiamine could correct the upregulated expression of P2X7 receptor induced under high FFA condition in HUVECs, and consequently suppressed oxidative stress and inflammatory responses.

scholarly journals Turnover of eicosanoid precursor fatty acids among phospholipid classes and subclasses of cultured human umbilical vein endothelial cells

1989 ◽  
Vol 258 (2) ◽  
pp. 427-434 ◽  
Author(s):  
H Takayama ◽  
M H Kroll ◽  
M A Gimbrone ◽  
A I Schafer
Keyword(s):  
Fatty Acids ◽  
Endothelial Cells ◽  
Umbilical Vein ◽  
Ionophore A23187 ◽  
Human Umbilical Vein ◽  
Phospholipid Classes ◽  
Specific Increase ◽  
Umbilical Vein Endothelial Cells ◽  
Relationship Of ◽  
The Relationship

Using cultured human umbilical vein endothelial cells, in which phosphatidylcholine (PC) is equally pulse-labelled by various eicosanoid precursor fatty acids (EPFAs), we have studied the remodelling of EPFAs among the phospholipid classes and subclasses with and without activation, and the relationship of this remodelling process to the selective release of arachidonic acid (AA) by phospholipase A2-mediated cell stimulation. When endothelial cells are pulse-incubated with radiolabelled EPFA for 15 min, greater than 80% of cell-associated radioactivity is present in phospholipids, among which greater than 60% is found in 1,2-diacyl-sn-glycero-3-phosphocholine (diacyl PC). After removing unincorporated radioactivity, reincubation of the pulse-labelled cells for up to 6 h results in progressive decrease in EPFA-labelled diacyl PC, increase in AA- or eicosapentaenoic acid (EPA)-labelled 1-O-alk-1-enyl-2-acyl-sn-glycero-3-phosphoethanolamine (plasmalogen PE) and increase only in AA-labelled 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkyl PC). This redistribution of radiolabelled phospholipids is not altered by the presence of excess non-radiolabelled EPFAs. When aspirin-treated EPFA-labelled endothelial cells are stimulated with ionophore A23187, a very selective release of AA is noted in comparison with eicosatrienoate (ETA) or EPA, accompanied by an equivalent decrease in AA-labelled diacyl PC and specific increase in AA-labelled plasmalogen PE and alkyl PC. These selective changes in AA radioactivity induced by A23187 are enhanced 2-fold by pretreating the AA-labelled cells with phorbol 12-myristate 13-acetate, which by itself induces no changes. The changes in radioactivity induced by A23187 without and with phorbol ester among the released AA, the diacyl PC and the plasmalogen PE are significantly correlated with each other. These results indicate that human endothelial cells incorporate EPFAs (AA, ETA, EPA) equally into diacyl PC but selectively release AA esterified into diacyl PC with specific remodelling into plasmalogen PE and alkyl PC.

Factor Xa inhibits HMGB1-induced septic responses in human umbilical vein endothelial cells and in mice

2014 ◽  
Vol 112 (10) ◽  
pp. 757-769 ◽  
Author(s):  
Wonhwa Lee ◽  
Sae-Kwang Ku ◽  
Jong-Sup Bae
Keyword(s):  
Endothelial Cells ◽  
Nuclear Dna ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Cecal Ligation ◽  
Post Treatment ◽  
Coagulation Cascade ◽  
Factor X ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

SummaryNuclear DNA-binding protein high mobility group box 1 (HMGB1) acts as a late mediator of severe vascular inflammatory conditions, such as sepsis. Activated factor X (FXa) is an important player in the coagulation cascade responsible for thrombin generation, and it influences cell signalling in various cell types by activating protease-activated receptors (PARs). However, the effect of FXa on HMGB1-induced inflammatory response has not been studied. First, we addressed this issue by monitoring the effects of post-treatment with FXa on lipopolysaccharide (LPS)- and cecal ligation and puncture (CLP)-mediated release of HMGB1 and HMGB1-mediated regulation of pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and septic mice. Post-treatment with FXa was found to suppress LPS-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangements. FXa also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in septic mice. In addition, FXa inhibited the production of tumour necrosis factor-α and interleukin (IL)-1β. FXa also facilitated the downregulation of CLP-induced release of HMGB1, production of IL-6, and mortality. Collectively, these results suggest that FXa may be regarded as a candidate therapeutic agent for treating vascular inflammatory diseases by inhibiting the HMGB1 signalling pathway.

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