Ambrozova, Gabriela ORCID: 0000-0002-8172-9746, Fidlerova, Tana, Verescakova, Hana, Koudelka, Adolf
ORCID: 0000-0002-9998-8383, Rudolph, Tanja K., Woodcock, Steven R., Freeman, Bruce A., Kubala, Lukas
ORCID: 0000-0002-7729-7338 and Pekarova, Michaela
(2016).
Nitro-oleic acid inhibits vascular endothelial inflammatory responses and the endothelial-mesenchymal transition.
Biochim. Biophys. Acta-Gen. Subj., 1860 (11).
S. 2428 - 2438.
AMSTERDAM:
ELSEVIER.
ISSN 1872-8006
Abstract
Background: Inflammatory-mediated pathological processes in the endothelium arise as a consequence of the dysregulation of vascular homeostasis. Of particular importance are mediators produced by stimulated monocytes/macrophages inducing activation of endothelial cells (ECs). This is manifested by excessive soluble pro-inflammatory mediator production and cell surface adhesion molecule expression. Nitro-fatty acids are endogenous products of metabolic and inflammatory reactions that display immuno-regulatory potential and may represent a novel therapeutic strategy to treat inflammatory diseases. The purpose of our study was to characterize the effects of nitro-oleic acid (OA-NO2) on inflammatory responses and the endothelial-mesenchymal transition (EndMT) in ECs that is a consequence of the altered healing phase of the immune response. Methods: The effect of OA-NO2 on inflammatory responses and EndMT was determined in murine macrophages and murine and human ECs using Western blotting, ELISA, immunostaining, and functional assays. Results: OA-NO2 limited the activation of macrophages and ECs by reducing pro-inflammatory cytokine production and adhesion molecule expression through its modulation of STAT. MAPK and NF-kappa B-regulated signaling. OA-NO2 also decreased transforming growth factor-beta-stimulated EndMT and pro-fibrotic phenotype of ECs. These effects are related to the downregulation of Smad2/3. Conclusions: The study shows the pleiotropic effect of OA-NO2 on regulating EC-macrophage interactions during the immune response and suggests a role for OA-NO2 in the regulation of vascular endothelial immune and fibrotic responses arising during chronic inflammation. General significance: These findings propose the OA-NO2 may be useful as a novel therapeutic agent for treatment of cardiovascular disorders associated with dysregulation of the endothelial immune response. (C) 2016 Elsevier B.V. All rights reserved.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-258055 | ||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1016/j.bbagen.2016.07.010 | ||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Biochim. Biophys. Acta-Gen. Subj. | ||||||||||||||||||||||||||||||||||||||||
Volume: | 1860 | ||||||||||||||||||||||||||||||||||||||||
Number: | 11 | ||||||||||||||||||||||||||||||||||||||||
Page Range: | S. 2428 - 2438 | ||||||||||||||||||||||||||||||||||||||||
Date: | 2016 | ||||||||||||||||||||||||||||||||||||||||
Publisher: | ELSEVIER | ||||||||||||||||||||||||||||||||||||||||
Place of Publication: | AMSTERDAM | ||||||||||||||||||||||||||||||||||||||||
ISSN: | 1872-8006 | ||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||
Uncontrolled Keywords: |
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Refereed: | Yes | ||||||||||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/25805 |
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