Abstract
ObjectivesPatients with rheumatoid arthritis (RA) display an increased risk of heart failure independent of traditional cardiovascular risk factors. To elucidate myocardial disease in RA, we have investigated molecular and cellular remodelling of the heart in an established mouse model of RA.MethodsThe collagen antibody-induced arthritis (CAIA) RA mouse model is characterised by joint inflammation and increased inflammatory markers in the serum. We used CAIA mice in the postinflammatory phase that resembles medically controlled RA or RA in remission. Hearts were collected for cardiomyocyte isolation, biochemistry and histology analysis.ResultsHearts from mice subjected to CAIA displayed hypertrophy (heart/body weight, mean±SD: 5.9±0.8vs 5.1±0.7 mg/g, p<0.05), fibrosis and reduced left ventricular fractional shortening compared with control. Cardiomyocytes from CAIA mice showed reduced cytosolic [Ca2+]i transient amplitudes (F/F0, mean±SD: 3.0±1.2vs 3.6±1.5, p<0.05) that was linked to reductions in sarcoplasmic reticulum (SR) Ca2+ store (F/F0, mean±SD: 3.5±1.3vs 4.4±1.3, p<0.01) measured with Ca2+ imaging. This was associated to lower fractional shortening in the cardiomyocytes from the CAIA mice (%FS, mean±SD: 3.4±2.2 vs 4.6%±2.3%, p<0.05). Ca2+ handling proteins displayed oxidation-dependent posttranslational modifications that together with an increase in superoxide dismutase expression indicate a cell environment with oxidative stress.ConclusionsThis study shows that inflammation during active RA has long-term consequences on molecular remodelling and contractile function of the heart, which further supports that rheumatology patients should be followed for development of heart failure.
Funder
Stockholm County Council
EU Project FP7-Health-2013-Innovation
Swedish Heart Lung Foundation
Knut och Alice Wallenbergs Stiftelse
Vetenskapsrådet
The Swedish Society for Medical Research
Stiftelsen Lars Hiertas Minne
Ragnar Söderberg Foundation
Subject
Cardiology and Cardiovascular Medicine
Cited by
29 articles.
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