Informace o publikaci
Nitro-oleic acid inhibits vascular endothelial inflammatory responses and the endothelial-mesenchymal transition
| Autoři | |
|---|---|
| Rok publikování | 2016 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://www.ncbi.nlm.nih.gov/pubmed/27431604 |
| Doi | http://dx.doi.org/10.1016/j.bbagen.2016.07.010 |
| Klíčová slova | Nitro-fatty acids; Nitro-oleic acid; Endothelial cells; Macrophages; Vascular inflammation; Endothelial-mesenchymal transition |
| Popis | 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. |