Universität zu Köln

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

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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
Creators:	Creators Email ORCID ORCID Put Code Ambrozova, Gabriela UNSPECIFIED orcid.org/0000-0002-8172-9746 UNSPECIFIED Fidlerova, Tana UNSPECIFIED UNSPECIFIED UNSPECIFIED Verescakova, Hana UNSPECIFIED UNSPECIFIED UNSPECIFIED Koudelka, Adolf UNSPECIFIED orcid.org/0000-0002-9998-8383 UNSPECIFIED Rudolph, Tanja K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Woodcock, Steven R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Freeman, Bruce A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubala, Lukas UNSPECIFIED orcid.org/0000-0002-7729-7338 UNSPECIFIED Pekarova, Michaela UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language NITRATED FATTY-ACIDS; FIBROBLAST-SPECIFIC PROTEIN-1; OXIDE SYNTHASE; TNF-ALPHA; CELLS; MACROPHAGES; ACTIVATION; MECHANISMS; EXPRESSION; MARKERS Multiple languages Biochemistry & Molecular Biology; Biophysics Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25805