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Human stanniocalcin-1 blocks TNF-alpha-induced monolayer permeability in human coronary artery endothelial cells.

ABSTRACT: Our previous studies revealed upregulation of stanniocalcin-1 (STC1) in cardiac vessels in dilated cardiomyopathy. However, the functional significance of STC1 is unknown. The objective of this study was to determine the effects of STC1 on TNF-alpha-induced monolayer permeability of human coronary artery endothelial cells (HCAECs).Cells were pretreated with STC1 for 30 minutes followed by treatment with TNF-alpha (2 ng/mL) for 24 hours. Monolayer permeability was studied using a transwell system. STC1 pretreatment significantly blocked TNF-alpha-induced monolayer permeability in a concentration- and time-dependent manner. STC1 effectively blocked TNF-alpha-induced downregulation of endothelial tight junction proteins zonula occluden-1 and claudin-1 at both mRNA and protein levels. STC1 also significantly decreased TNF-alpha-induced superoxide anion production. The inhibitory effect of STC1 was specific to TNF-alpha, as it failed to inhibit VEGF-induced endothelial permeability. Furthermore, STC1 partially blocked NF-kappaB and JNK activation in TNF-alpha-treated endothelial cells. JNK inhibitor and antioxidant also effectively blocked TNF-alpha-induced NF-kappaB activation and monolayer permeability in HCAECs.STC1 maintains endothelial permeability in TNF-alpha-treated HCAECs through preservation of tight junction protein expression, suppression of superoxide anion production, and inhibition of the activation of NFkappaB and JNK, suggesting an important role for STC1 in regulating endothelial functions during cardiovascular inflammation.

SUBMITTER: Chen C

PROVIDER: S-EPMC2731718 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Human stanniocalcin-1 blocks TNF-alpha-induced monolayer permeability in human coronary artery endothelial cells.

Chen Changyi C Jamaluddin Md Saha MS Yan Shaoyu S Sheikh-Hamad David D Yao Qizhi Q

Arteriosclerosis, thrombosis, and vascular biology 20080228 5

<h4>Objective</h4>Our previous studies revealed upregulation of stanniocalcin-1 (STC1) in cardiac vessels in dilated cardiomyopathy. However, the functional significance of STC1 is unknown. The objective of this study was to determine the effects of STC1 on TNF-alpha-induced monolayer permeability of human coronary artery endothelial cells (HCAECs).<h4>Methods and results</h4>Cells were pretreated with STC1 for 30 minutes followed by treatment with TNF-alpha (2 ng/mL) for 24 hours. Monolayer per ...[more]

PMID: 18309109

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Project description:Background and Objectives: Tumor necrosis factor alpha (TNF-α) is proatherogenic and associated with the risk of acute ischemic events, although the mechanisms that regulate TNF-α expression in stable coronary artery disease (SCAD) are not fully understood. We investigated whether metabolic, inflammatory, and epigenetic (microRNA (miRNA)) markers are associated with TNF-α expression in SCAD. Materials and Methods: Patients with SCAD were prospectively recruited and their metabolic and inflammatory profiles were assessed. TNF-α levels were assessed using an enzyme-linked immunosorbent assay. The relative expression of six circulating miRNAs associated with the regulation of inflammation and/or atherosclerosis was determined. Results: Of the 24 included patients with the mean age of 65 (9) years, 88% were male, and 54% were diabetic. The TNF-α levels were (median (interquartile range)) 1.0 (0.7-1.1) pg/mL. The percentage of glycosylated hemoglobin (r = 0.418, p = 0.042), serum triglyceride levels (r = 0.429, p = 0.037), and C-reactive protein levels (r = 0.407, p = 0.048) were positively correlated with TNF-α levels. Of the candidate miRNAs, miR-146a expression levels were negatively correlated with TNF-α levels (as indicated by r = 0.500, p = 0.035 for correlation between delta cycle threshold (ΔCt) miR-146a and TNF-α levels). In multivariate analysis, serum triglyceride levels and miR-146a expression levels were independently associated with TNF-α levels. miR-146 expression levels were not associated with metabolic or other inflammatory parameters and were negatively correlated with the number of coronary vessels with obstructive disease (as indicated by r = 0.556, p = 0.017 for correlation between ΔCt miR-146a and number of diseased vessels). Conclusions: miR-146a expression levels were negatively correlated with TNF-α levels in patients with SCAD, irrespective of other metabolic or inflammatory markers, and with the severity of coronary artery disease. The results add to the knowledge on the role of miR-146a in TNF-α-based inflammation in SCAD and support future research on the potential therapeutic use of miR-146a in such a clinical scenario.

Dataset Information

Human stanniocalcin-1 blocks TNF-alpha-induced monolayer permeability in human coronary artery endothelial cells.

Publications

Human stanniocalcin-1 blocks TNF-alpha-induced monolayer permeability in human coronary artery endothelial cells.

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