Dataset Information

Tumor Necrosis Factor-Alpha and the ERK Pathway Drive Chemerin Expression in Response to Hypoxia in Cultured Human Coronary Artery Endothelial Cells.

ABSTRACT:

Background

Chemerin, a novel adipokine, plays a role in the inflammation status of vascular endothelial cells. Hypoxia causes endothelial-cell proliferation, migration, and angiogenesis. This study was aimed at evaluating the protein and mRNA expression of chemerin after exposure of human coronary artery endothelial cells (HCAECs) to hypoxia.

Methods and results

Cultured HCAECs underwent hypoxia for different time points. Chemerin protein levels increased after 4 h of hypoxia at 2.5% O2, with a peak of expression of tumor necrosis factor-alpha (TNF-alpha) at 1 h. Both hypoxia and exogenously added TNF-alpha during normoxia stimulated chemerin expression, whereas an ERK inhibitor (PD98059), ERK small interfering RNA (siRNA), or an anti-TNF-alpha antibody attenuated the chemerin upregulation induced by hypoxia. A gel shift assay indicated that hypoxia induced an increase in DNA-protein binding between the chemerin promoter and transcription factor SP1. A luciferase assay confirmed an increase in transcriptional activity of SP1 on the chemerin promoter during hypoxia. Hypoxia significantly increased the tube formation and migration of HCAECs, whereas PD98059, the anti-TNF-alpha antibody, and chemerin siRNA each attenuated these effects.

Conclusion

Hypoxia activates chemerin expression in cultured HCAECs. Hypoxia-induced chemerin expression is mediated by TNF-alpha and at least in part by the ERK pathway. Chemerin increases early processes of angiogenesis by HCAECs after hypoxic treatment.

SUBMITTER: Chua SK

PROVIDER: S-EPMC5085022 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tumor Necrosis Factor-Alpha and the ERK Pathway Drive Chemerin Expression in Response to Hypoxia in Cultured Human Coronary Artery Endothelial Cells.

Chua Su-Kiat SK Shyu Kou-Gi KG Lin Yuh-Feng YF Lo Huey-Ming HM Wang Bao-Wei BW Chang Hang H Lien Li-Ming LM

PloS one 20161028 10

<h4>Background</h4>Chemerin, a novel adipokine, plays a role in the inflammation status of vascular endothelial cells. Hypoxia causes endothelial-cell proliferation, migration, and angiogenesis. This study was aimed at evaluating the protein and mRNA expression of chemerin after exposure of human coronary artery endothelial cells (HCAECs) to hypoxia.<h4>Methods and results</h4>Cultured HCAECs underwent hypoxia for different time points. Chemerin protein levels increased after 4 h of hypoxia at 2 ...[more]

PMID: 27792771

Similar Datasets

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.

Project description:BackgroundAdipokine chemerin was proven to be associated with coronary artery disease (CAD), but its prognostic implications in CAD remain unclear.MethodsThis study consists of two parts, one is a basic study and the other is a clinical cohort study. First, we investigated the differential expression of six adipokines in the atherosclerotic mice model compared to mice with milder degrees of atherosclerosis and mice without atherosclerosis using microarray data. We then examined the potential of chemerin as a diagnostic and prognostic indicator in a CAD cohort. A total of 152 patients were enrolled in our study, including 77 patients with angiographically proven CAD and 75 control subjects without cardiovascular disease. Plasma adipokine chemerin levels were measured in all patients, and major adverse cardiovascular events (MACEs) were followed up, including ischemic stroke, non-fatal myocardial infarction, revascularization, and cardiovascular death.ResultsIn the aortas of atherosclerotic mice, chemerin expression was up-regulated compared to control mice. The plasma chemerin levels of CAD patients were higher than those of non-CAD patients (128.93 ± 37.06 vs. 109.85 ± 27.47 mmol/L, respectively, P < 0.001). High chemerin levels were an independent predictor of CAD (β = 2.702, 95% CI, 1.344-5.431, P = 0.001). We followed up with patients for a median duration of 5.5 years (3.9-5.6). The Kaplan-Meier curves showed that patients in the high chemerin group had a significantly higher risk of MACEs than the low chemerin group in patients with CAD (log-rank P = 0.003), not with non-CAD (Log-rank P = 0.120). Furthermore, Cox multivariate analysis revealed that high chemerin levels were an independent predictor of MACEs (HR 2.267; 95% CI, 1.139-4.515; P = 0.020). Finally, the cellular study showed that chemerin is predominantly expressed in PBMC-derived macrophages.ConclusionPlasma chemerin levels were increased in the CAD patients, and a high chemerin level increased the risk of MACEs in CAD patients.

Dataset Information

Tumor Necrosis Factor-Alpha and the ERK Pathway Drive Chemerin Expression in Response to Hypoxia in Cultured Human Coronary Artery Endothelial Cells.

Background

Methods and results

Conclusion

Publications

Tumor Necrosis Factor-Alpha and the ERK Pathway Drive Chemerin Expression in Response to Hypoxia in Cultured Human Coronary Artery Endothelial Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets