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

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.