Objectives Patients 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.
Methods The 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.
Results Hearts 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.
Conclusions This 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.
- heart disease
- heart failure
- translational cardiovascular science
- myocardial disease basic science
- cardiac risk factors and prevention
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Contributors GP contributed to study conception and design, acquisition of the data, analysis and interpretation of the data and drafting the article. DCA contributed to study conception, analysis and interpretation of the data and writing the article. CIS contributed in acquisition and interpretation of the data. LHL contributed to analysing and interpreting the data. AB-F, NMA, KS, TF-Z and AJ contributed in acquiring and analysing the data. All the authors contributed in revising the article critically for important intellectual content. All the authors approved the final version of the article to be published.
Funding This work was supported by the Lars Hiertas foundation to GP (FO20150396), the Swedish Heart Lung Foundation (20160741 and 20150651), the Stockholm County Council (20120687), Åke Wiberg Foundation, The Jeansson Foundation and The Swedish Society for Medical Research to DCA, the Swedish Research Council (542-2013-8373), Knut and Alice Wallenberg Foundation, Ragnar Söderberg Foundation and EU Project FP7-Health-2013-Innovation (1602919-2) to CIS, the Swedish Heart Lung Foundation (20150557) and Swedish Research Council grants (523-2014-2336 and 2013-23897-104604-23) to LHL.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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