Identifying a marked inflammation mediated cardiac dysfunction during the development of arthritis in collagen-induced arthritis mice

Systemic inflammation is very closely linked to the increased risk of cardiovascular diseases (CVD) in rheumatoid arthritis (RA). We investigated the cardiac changes during the development of arthritis in collagen-induced arthritis (CIA) mice to explore the potential role of inflammation on cardiac dysfunction in RA.Arthritis severity was evaluated using clinical indices, micro-computed tomography and histopathology. Cardiac function was determined by transthoracic echocardiography at weeks 5, 7, 9 and 11 after immunisation in mice. At week 7 (day 50), mice joints and hearts were removed for pathological study, and cardiomyocytes and cardiac fibroblasts were isolated using Langendorff perfusion method ex vivo to measure the expression of inflammatory and cardiac-related genes by real time PCR. The expression of key molecule in cardiac dysfunction (β-MHC) was also tested in H9c2 cardiomyocyte treated with sera derived from CIA mice or RA patients.At day 50 after immunisation, cardiac function in CIA mice was prominently reduced as evidenced by decreased ejection fraction (EF) and fractional shortening (FS), increased left ventricular end-systolic volume (LVESV) and internal systolic diameter (LVIDs). Accordingly, enhanced inflammatory cell infiltration and fibrosis were identified in ventricular tissues pathologically, and increased inflammatory gene expression including TNF-α, IL-6, IL-17 and MMP3 was detected in isolated ventricular cardiomyocytes and cardiac fibroblasts from CIA mice. Furthermore, H9c2 cells treated with sera from CIA mice or RA patients exhibited high levels of β-MHC.Joint inflammation is associated with an obvious cardiac dysfunction and enhanced inflammation infiltration and inflammatory cytokine production in cardiomyocytes and cardiac fibroblasts during CIA development. Our data provide the direct evidence that inflammation contributes to the development of cardiac diseases in RA patients.