SAT0026 Differential levels of il-7 expression in adventitia of non-ra and ra patients with coronary artery disease

Abstract

BackgroundRheumatoid Arthritis (RA) patients have increased cardiovascular risk due to accelerated atherosclerosis (ATS), which significantly contributes to excess mortality in RA1. The increased cardiovascular risk cannot be fully explained by traditional risk factors and systemic chronic inflammation appears to play a crucial role. Interestingly, IL-7, a proinflammatory cytokine involved in RA pathogenesis, appears to play a role also in atherosclerosis2 but its effect on cardiovascular disease (CVD) in RA has not been studied yet.ObjectivesTo examine serum IL-7 levels and expression of IL-7, IL-7R, CD3 and CD20 in aortic adventitia of RA and non-RA patients with coronary artery disease (CAD) and to search for relationships between systemic IL-7 levels and expression of vascular markers, cardiovascular risk factors including metabolic and inflammatory markers.MethodsWe examined 19 RA patients and 20 non-RA patients undergoing coronary artery bypass graft surgery included in the Feiring Heart Biopsy Study. Serum IL-7 levels were measured by chemiluminescence (MSD). Biopsies from the adventitia of thoracic aorta from a subset of patients (12 RA and 14 non-RA) were stained for IL-7, IL-7R, CD3 and CD20 by immunohistochemistry and scored per mm2 of tissue.ResultsNon-RA patients had lower IL-7 serum levels than RA (3.4±3.3 vs. 6.7±3.5, p<0.05). Independently of RA diagnosis, IL-7 significantly correlated with CRP (rho=0.450, p=0.008), triglycerides (TG, rho=0.566, p=0.005), glucose (rho=0.642, p=0.001) and hypertension (p=0.036). Levels of IL-7 were associated with New York Heart Association class (rho=0.429, p=0.014) and this was stronger in non-RA patients (rho=0.577, p=0.010). No associations were found with smoking or markers of CVD severity (i.e. numbers of arteries with significant stenosis or number of previous myocardial infarcts (MI)).The number of IL-7 +and IL-7R+cells/mm2 in adventitia were significantly higher in RA (134.2±45.5 and 144±49.9 respectively) than non-RA patients (46.9±22.8 and 54.4±20.2, p<0.005) and were associated with serum IL-7 levels (rho=0.551 and rho=0.588, p<0.01). Both IL-7 +and IL7R+cells were associated with a positive history of MI (p=0.047 and p=0.005) and IL-7R+cells with the number of previous MIs (rho=0.408, p=0.038). Only in RA patients, IL-7R+cells showed a trend for correlation with TG (rho=0.771, p=0.072). IL-7 +and IL-7R+cells correlated with CD3 (rho=0.688, p=0.013 and rho=0.630 p=0.028), but no correlation was found with CD20. Cholesterol and HDL levels were associated with IL-7 +cells only in non-RA patients (rho=0.729 p=0.04 and rho=0.733, p=0.038).ConclusionsAmong patients with CAD, those with RA had higher serum IL-7 and a greater expression of both IL-7/IL-7R is aortic adventitia. Systemic levels of IL-7 were related to its vascular expression. Thus, the IL-7/IL-7R axis may play a role in the accelerated atherogenesis observed in RA; further studies are needed to elucidate the precise role of IL-7 and impact of potential IL-7R blockade in CV risk in RA.References[1...

SAT0023 Control of cytokine mrna degradation by the histone deacetylase inhibitor itf2357 in rheumatoid arthritis fibroblast-like synoviocytes

“…1 In rheumatoid arthritis (RA), altered expression of the mRNA-degrading protein TTP (tristetraprolin, ZFP36) has been recently reported in synovial tissue, possibly contributing to the perpetuating inflammatory loop in the synovium. 2 Histone deacetylase inhibitors (HDACi) are small molecule drugs suppressing cytokine production in vitro and in vivo and displaying initial safety and efficacy in the treatment of systemic onset juvenile idiopathic arthritis. 3,4 However, their transcriptional and post-transcriptional mechanisms of action are not yet completely characterised.…”