Garlic metabolites fail to inhibit the activation of the transcription factor NF-kappaB and subsequent expression of the adhesion molecule E-selectin in human endothelial cells

Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a comprehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miRNA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17β-estradiol (E2) (1 nmol/L, 24 h). miRNA–mRNA pairings and their associated canonical pathways were determined using Ingenuity Pathway Analysis software. Transcription factors were identified among the miRNA-regulated genes. Transcription factor downstream target genes were predicted by consensus transcription factor binding sites in the promoter region of E2-regulated genes by using JASPAR and TRANSFAC tools in Enrichr software. Results: miRNA–target pairings were filtered by using differentially expressed miRNAs and mRNAs characterized by a regulatory relationship according to miRNA target prediction databases. The analysis identified 588 miRNA–target interactions between 102 miRNAs and 588 targets. Specifically, 63 upregulated miRNAs interacted with 295 downregulated targets, while 39 downregulated miRNAs were paired with 293 upregulated mRNA targets. Functional characterization of miRNA/mRNA association analysis highlighted hypoxia signaling, integrin, ephrin receptor signaling and regulation of actin-based motility by Rho among the canonical pathways regulated by E2 in HUVEC. Transcription factors and downstream genes analysis revealed eight networks, including those mediated by JUN and REPIN1, which are associated with cadherin binding and cell adhesion molecule binding pathways. Conclusion: This study identifies regulatory networks obtained by integrative microarray analysis and provides additional insights into the way estradiol could regulate endothelial function in human endothelial cells.

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Alterations in intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in human endothelial cells

Tissue and Cell ◽

10.1016/j.tice.2018.09.002 ◽

2018 ◽

Vol 54 ◽

pp. 139-143 ◽

Cited By ~ 15

Author(s):

Khaled Habas ◽

Lijun Shang

Keyword(s):

Endothelial Cells ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Intercellular Adhesion Molecule ◽

Vascular Cell Adhesion ◽

Human Endothelial Cells ◽

Intercellular Adhesion Molecule 1 ◽

Vascular Cell ◽

Cell Adhesion Molecule 1

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Direct Activation of Human Endothelial Cells by Plasmodium falciparum-Infected Erythrocytes

Infection and Immunity ◽

10.1128/iai.73.6.3271-3277.2005 ◽

2005 ◽

Vol 73 (6) ◽

pp. 3271-3277 ◽

Cited By ~ 37

Author(s):

Nicola K. Viebig ◽

Ulrich Wulbrand ◽

Reinhold Förster ◽

Katherine T. Andrews ◽

Michael Lanzer ◽

...

Keyword(s):

Endothelial Cells ◽

Plasmodium Falciparum ◽

Endothelial Cell ◽

Adhesion Molecule ◽

Cell Activation ◽

Physical Contact ◽

Intercellular Adhesion Molecule ◽

Immune Reactivity ◽

Human Endothelial Cells ◽

Tnf Α

ABSTRACT Cytoadherence of Plasmodium falciparum-infected erythrocytes (PRBC) to endothelial cells causes severe clinical disease, presumably as a of result perfusion failure and tissue hypoxia. Cytoadherence to endothelial cells is increased by endothelial cell activation, which is believed to occur in a paracrine fashion by mediators such as tumor necrosis factor alpha (TNF-α) released from macrophages that initially recognize PRBC. Here we provide evidence that PRBC directly stimulate human endothelial cells in the absence of macrophages, leading to increased expression of adhesion-promoting molecules, such as intercellular adhesion molecule 1. Endothelial cell stimulation by PRBC required direct physical contact for a short time (30 to 60 min) and was correlated with parasitemia. Gene expression profiling of endothelial cells stimulated by PRBC revealed increased expression levels of chemokine and adhesion molecule genes. PRBC-stimulated endothelial cells especially showed increased expression of molecules involved in parasite adhesion but failed to express molecules promoting leukocyte adhesion, such as E-selectin and vascular cell adhesion molecule 1, even after challenge with TNF-α. Collectively, our data suggest that stimulation of endothelial cells by PRBC may have two effects: prevention of parasite clearance through increased cytoadherence and attenuation of leukocyte binding to endothelial cells, thereby preventing deleterious immune reactivity.

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PS204. Mechanical (or “Gravitational”) Unloading Reduces Inflammatory and Cell Adhesion Molecule Gene Expression in Human Endothelial Cells

Journal of Vascular Surgery ◽

10.1016/j.jvs.2012.03.197 ◽

2012 ◽

Vol 55 (6) ◽

pp. 78S-79S

Author(s):

Marlene Grenon ◽

Jesus Aguado-Zunega ◽

Michael S. Conte ◽

Millie Hughes-Fulford

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Human Endothelial Cells ◽

Gravitational Unloading ◽

Adhesion Molecule Gene

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Molecular Dissection of the Transcriptional Control of Intracellular Adhesion Molecule-1 (ICAM-1) Promoter in Human Endothelial Cells by Mineralocorticoid Receptor

10.1210/endo-meetings.2011.part2.p12.p1-576 ◽

2011 ◽

pp. P1-576-P1-576

Author(s):

Vincenzo Marzolla ◽

Andrea Armani ◽

Antonella Antelmi ◽

Caterina Mammi ◽

Matilde Calanchini ◽

...

Keyword(s):

Endothelial Cells ◽

Adhesion Molecule ◽

Mineralocorticoid Receptor ◽

Transcriptional Control ◽

Molecular Dissection ◽

Human Endothelial Cells ◽

Intracellular Adhesion Molecule

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Suppressive Effects of the Gynura bicolor Ether Extract on Endothelial Permeability and Leukocyte Transmigration in Human Endothelial Cells Induced by TNF-α

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9413724 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Shu-Ling Hsieh ◽

Jyh-Jye Wang ◽

Kuan-Hua Su ◽

Ying-Lan Kuo ◽

Shuchen Hsieh ◽

...

Keyword(s):

Endothelial Cells ◽

Adhesion Molecule ◽

Far East ◽

Endothelial Permeability ◽

Intercellular Adhesion Molecule ◽

Ether Extract ◽

Human Endothelial Cells ◽

Tnf Α ◽

Ea.Hy926 Cells ◽

Gynura Bicolor

Gynura bicolor (Roxb. and Willd.) DC (G. bicolor) is generally used as a dietary vegetable and traditional herb in Taiwan and the Far East. G. bicolor exerts antioxidant and anti-inflammatory effects and regulates blood lipids and cholesterol. However, the effects of G. bicolor on endothelial transmigration and atherosclerosis are not clear. The present study investigated the effects of G. bicolor on endothelial permeability and transmigration in human endothelial cells. We prepared G. bicolor ether extract (GBEE) for use as the experimental material. Under TNF-α stimulation, HL-60 cell adherence to EA.hy926 cells, the shape of EA.hy926 cells, and the expression of adhesion molecules and transmigration-related regulatory molecules were analysed after pretreatment with GBEE for 24 h. GBEE inhibited leukocyte adhesion to endothelial cells, reduced intercellular adhesion molecule-1 (ICAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) expressions, and decreased endothelial monolayer permeability. GBEE also reduced paracellular transmigration by reducing the levels of reactive oxygen species (ROS), Src phosphorylation, and vascular endothelial-cadherin (VE-cadherin) phosphorylation. GBEE reduced transcellular migration via inhibition of Ras homolog family member A (RhoA) and Rho-associated protein kinase (ROCK) expression and phosphorylation of the ezrin-radixin-moesin (ERM) protein. Incubation of EA.hy926 cells with GBEE for 8 h and stimulation with TNF-α for 3 h reduced the phosphorylation of the inhibitor of kappa B (IĸB) and DNA-binding activity of nuclear factor-ĸB (NF-ĸB). These results suggest that GBEE has a protective effect against endothelial dysfunction via suppression of leukocyte-endothelium adhesion and transmigration.

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