Total calcium-sensing receptor expression in circulating monocytes is increased in rheumatoid arthritis patients with severe coronary artery calcification.

Julien Paccou,Cédric Boudot,Patrice Fardellone,Michel Brazier,Cédric Renard,Ziad Massy,Said Kamel,Sophie Liabeuf,Romuald Mentaverri

doi:10.1186/s13075-014-0412-5

Abstract

IntroductionHuman circulating monocytes express the calcium-sensing receptor (CaSR) and are involved in atherosclerosis. This study investigated the potential association between vascular calcification in rheumatoid arthritis (RA) and CaSR expression in circulating monocytes.MethodsIn this cross-sectional study, 50 RA patients were compared to 25 control subjects matched for age and gender. Isolation of peripheral blood mononuclear cells and flow cytometry analysis were performed to study the surface and total CaSR expression in circulating monocytes. Coronary artery calcium (CAC) and abdominal aortic calcification (AAC) scores were evaluated by computed tomography and an association between these scores and the surface and/or total CaSR expression in circulating monocytes in RA patients was investigated.ResultsThe two groups were similar in terms of age (RA: 60.9 ± 8.3 years, versus controls: 59.6 ± 5.3 years) and gender (RA: 74.0% females versus 72.0% females). We did not find a higher prevalence and greater burden of CAC or AAC in RA patients versus age- and gender-matched controls. When compared with control subjects, RA patients did not exhibit greater total CaSR (101.6% ± 28.8 vs. 99.9% ± 22.0) or surface CaSR (104.6% ± 20.4 vs. 99.9% ± 13.7) expression, but total CaSR expression in circulating monocytes was significantly higher in RA patients with severe CAC (Agatston score ≥200, n = 11) than in patients with mild-to-moderate CAC (1 to 199, n = 21) (P = 0.01).ConclusionsThis study demonstrates for the first time that total CaSR expression in human circulating monocytes is increased in RA patients with severe coronary artery calcification.

Highlights

Human circulating monocytes express the calcium-sensing receptor (CaSR) and are involved in atherosclerosis
We provided evidence indicating that CaSR expression can be measured by flow cytometry in human circulating monocytes and its measurement would be potentially useful in certain clinical situations, in which changes in CaSR expression could be expected [28]
The mean duration of disease was greater than 12 years, more than one half of rheumatoid arthritis (RA) patients were treated by tumor necrosis factor alpha (TNFα) antagonists

Summary

Introduction

Human circulating monocytes express the calcium-sensing receptor (CaSR) and are involved in atherosclerosis. This study investigated the potential association between vascular calcification in rheumatoid arthritis (RA) and CaSR expression in circulating monocytes. The increased risk for cardiovascular disease cannot be fully explained by traditional cardiovascular risk factors [1,2]. Stratification tools such as the Framingham risk score [6], widely used in primary. Patients with RA are known to develop early-onset, widespread calcification in various vascular beds [13,14,15]. This is consistent with the concept whereby inflammation promotes atherosclerosis and vascular calcification [16]. Cardiovascular disease remains a major problem in RA patients and there is a need to focus on further delineating the underlying biological mechanisms involved in vascular calcification, and developing and evaluating novel biomarkers

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Conclusion