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Endothelial Dysfunction in Rheumatoid Arthritis: Mechanistic Insights and Correlation with Circulating Markers of Systemic Inflammation
OBJECTIVES: To determine mechanisms involved in endothelial dysfunction (ED) during the course of arthritis and to investigate the link between cytokines, chemokines and osteoprotegerin. APPROACH AND RESULTS: Experiments were conducted on aortic rings at day 4 (preclinical), day 11 (onset of disease...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711944/ https://www.ncbi.nlm.nih.gov/pubmed/26761790 http://dx.doi.org/10.1371/journal.pone.0146744 |
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author | Totoson, Perle Maguin-Gaté, Katy Nappey, Maude Wendling, Daniel Demougeot, Céline |
author_facet | Totoson, Perle Maguin-Gaté, Katy Nappey, Maude Wendling, Daniel Demougeot, Céline |
author_sort | Totoson, Perle |
collection | PubMed |
description | OBJECTIVES: To determine mechanisms involved in endothelial dysfunction (ED) during the course of arthritis and to investigate the link between cytokines, chemokines and osteoprotegerin. APPROACH AND RESULTS: Experiments were conducted on aortic rings at day 4 (preclinical), day 11 (onset of disease), day 33 (acute disease) and day 90 (chronic disease) after adjuvant-induced arthritis (AIA) in Lewis rats. At day 4, the unique vascular abnormality was a reduced norepinephrine-induced constriction. At day 11, endothelial function assessed by the relaxation to acetylcholine was normal despite increased cyclo-oxygenase-2 activity (COX-2) and overproduction of superoxide anions that was compensated by increased nitric oxide synthase (NOS) activity. At day 33, ED apparition coincides with the normalization of NOS activity. At day 90, ED was only observed in rats with a persisting imbalance between endothelial NOS and COX-2 pathways and higher plasma levels of IL-1β and TNFα. Plasma levels of IL-1β, TNFα and MIP-1α negatively correlated with Ach-induced relaxation throughout the course of AIA. CONCLUSIONS: Our data identified increased endothelial NOS activity as an important compensatory response that opposes the ED in the early arthritis. Thereafter, a cross-talk between endothelial COX-2/NOS pathways appears as an important element for the occurrence of ED. Our results encourage determining the clinical value of IL-1β, TNFα and MIP-1α as biomarkers of ED in RA. |
format | Online Article Text |
id | pubmed-4711944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-47119442016-01-26 Endothelial Dysfunction in Rheumatoid Arthritis: Mechanistic Insights and Correlation with Circulating Markers of Systemic Inflammation Totoson, Perle Maguin-Gaté, Katy Nappey, Maude Wendling, Daniel Demougeot, Céline PLoS One Research Article OBJECTIVES: To determine mechanisms involved in endothelial dysfunction (ED) during the course of arthritis and to investigate the link between cytokines, chemokines and osteoprotegerin. APPROACH AND RESULTS: Experiments were conducted on aortic rings at day 4 (preclinical), day 11 (onset of disease), day 33 (acute disease) and day 90 (chronic disease) after adjuvant-induced arthritis (AIA) in Lewis rats. At day 4, the unique vascular abnormality was a reduced norepinephrine-induced constriction. At day 11, endothelial function assessed by the relaxation to acetylcholine was normal despite increased cyclo-oxygenase-2 activity (COX-2) and overproduction of superoxide anions that was compensated by increased nitric oxide synthase (NOS) activity. At day 33, ED apparition coincides with the normalization of NOS activity. At day 90, ED was only observed in rats with a persisting imbalance between endothelial NOS and COX-2 pathways and higher plasma levels of IL-1β and TNFα. Plasma levels of IL-1β, TNFα and MIP-1α negatively correlated with Ach-induced relaxation throughout the course of AIA. CONCLUSIONS: Our data identified increased endothelial NOS activity as an important compensatory response that opposes the ED in the early arthritis. Thereafter, a cross-talk between endothelial COX-2/NOS pathways appears as an important element for the occurrence of ED. Our results encourage determining the clinical value of IL-1β, TNFα and MIP-1α as biomarkers of ED in RA. Public Library of Science 2016-01-13 /pmc/articles/PMC4711944/ /pubmed/26761790 http://dx.doi.org/10.1371/journal.pone.0146744 Text en © 2016 Totoson et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Totoson, Perle Maguin-Gaté, Katy Nappey, Maude Wendling, Daniel Demougeot, Céline Endothelial Dysfunction in Rheumatoid Arthritis: Mechanistic Insights and Correlation with Circulating Markers of Systemic Inflammation |
title | Endothelial Dysfunction in Rheumatoid Arthritis: Mechanistic Insights and Correlation with Circulating Markers of Systemic Inflammation |
title_full | Endothelial Dysfunction in Rheumatoid Arthritis: Mechanistic Insights and Correlation with Circulating Markers of Systemic Inflammation |
title_fullStr | Endothelial Dysfunction in Rheumatoid Arthritis: Mechanistic Insights and Correlation with Circulating Markers of Systemic Inflammation |
title_full_unstemmed | Endothelial Dysfunction in Rheumatoid Arthritis: Mechanistic Insights and Correlation with Circulating Markers of Systemic Inflammation |
title_short | Endothelial Dysfunction in Rheumatoid Arthritis: Mechanistic Insights and Correlation with Circulating Markers of Systemic Inflammation |
title_sort | endothelial dysfunction in rheumatoid arthritis: mechanistic insights and correlation with circulating markers of systemic inflammation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711944/ https://www.ncbi.nlm.nih.gov/pubmed/26761790 http://dx.doi.org/10.1371/journal.pone.0146744 |
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