Endothelial Dysfunction in Rheumatoid Arthritis: Mechanistic Insights and Correlation with Circulating Markers of Systemic InflammationReport as inadecuate




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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.



Author: Perle Totoson, Katy Maguin-Gaté, Maude Nappey, Daniel Wendling, Céline Demougeot

Source: http://plos.srce.hr/



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