Rheumatoid arthritis patients have a pro-atherogenic cytokine microenvironment in the aortic adventitia

Ahmed, A., Hollan, I., Curran, S. A., Kitson, S. M., Riggio, M. P. , Mikkelsen, K., Almdahl, S. M., Aukrust, P., McInnes, I. B. and Goodyear, C. S. (2016) Rheumatoid arthritis patients have a pro-atherogenic cytokine microenvironment in the aortic adventitia. Arthritis and Rheumatism, 68(6), pp. 1361-1366. (doi:10.1002/art.39574) (PMID:26749303) (PMCID:PMC4920270)

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Abstract

Background: People with rheumatoid arthritis (RA) are at increased risk of developing cardiovascular disease (CVD) via as yet, poorly defined mechanisms. Inflammatory pathways, in particular within the vascular adventitia, are implicated in primary CVD pathogenesis but could be amplified in RA at the local tissue level. We therefore examined aortic adventitial (AA) from coronary artery disease (CAD) patients with or without RA to determine the cytokine profile contained therein. Methods and Results: AA and internal mammary artery (IMA) biopsies from 19 RA patients and 20 non-RA patients undergoing coronary artery bypass graft surgery (CABG) were examined by immunohistochemistry. IL-18, IL-33 and Tumor Necrosis Factor (TNF) were expressed in AA biopsies in both groups, and their expression was significantly higher in RA patients. In RA patients, IL-33 expression in endothelial cells correlated positively with the number of swollen joints, suggesting a link between the systemic disease state and the local vascular tissue microlesion. Conclusions: The presence of pro-inflammatory cytokines IL-18, IL-33 and TNF may play a role in the inflammatory process within the adventitia that contributes to plaque formation and destabilization. In theory, the amplified expression of these cytokines may contribute to the known increased occurrence and severity of CAD in RA.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Kitson, Miss Susan and Goodyear, Professor Carl and Riggio, Dr Marcello
Authors: Ahmed, A., Hollan, I., Curran, S. A., Kitson, S. M., Riggio, M. P., Mikkelsen, K., Almdahl, S. M., Aukrust, P., McInnes, I. B., and Goodyear, C. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Arthritis and Rheumatism
Publisher:John Wiley & Sons, Inc.
ISSN:0004-3591
ISSN (Online):1529-0131
Published Online:26 May 2016
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Arthritis and Rheumatism 68(6): 1361-1366
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
443301RA-associated factors and their affect on B cell targeted cell deathCarl GoodyearArthritis Research UK (ARC)MP/17653III -IMMUNOLOGY
559981The simultaneous targeting of inflammatory and osteoglastogenic mechanisms in rheumatoid arthritisCarl GoodyearArthritis Research UK (ARUK)MP/19701III -IMMUNOLOGY