AB0146 IDENTIFICATION A MARKED INFLAMMATION MEDIATED CARDIAC DYSFUNCTION DURING THE DEVELOPMENT OF ARTHRITIS IN COLLAGEN INDUCED ARTHRITIS MICE. (June 2019)

• Record Type: Journal Article
• Authors: Wang, Fang; Luo, Aishu; Zhou, Zihao; Tan, Wenfeng
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 2
• Page Start: 1531
• Page End: 1531
• Publication Date: 2019-06
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2019-eular.4553
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Systemic inflammation is strong linked to the increased risk of cardiovascular diseases (CVD) in rheumatoid arthritis (RA) 1 . Increased cardiovascular risk in RA patients can not be fully explained by the traditional risk factors, such as hypertension, obesity, diabetes, age and smoking 2, 3 . Much more work is needed to elucidate the mechanism of chronic inflammation bridging RA and cardiovascular disease. Objectives: To investigate the cardiac changes during the development of arthritis in collagen induced arthritis (CIA) mice and to explore the potential role of inflammation on cardiac dysfunction in RA. Methods: Arthritis severity was evaluated using clinical indices, micro-computed tomography and histopathology. Cardiac function was determined by transthoracic echocardiography at week 5, 7, 9 and 11 after immunization 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 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. Results: At day 50 after immunization, 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 cells infiltration and fibrosis were identified in ventricular tissues pathologically, and increased inflammatory genes expression including TNF-α, IL-6, IL-17 and MMP3 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. Conclusion: Joint inflammation is associated with an obvious cardiac dysfunction and enhanced inflammation infiltration and inflammatory cytokines production in cardiomyocytes and cardiac fibroblasts during CIA development. Our data provide the direct evidence that inflammation contributes to development of cardiac diseases in RA patients. References: [1] SOLOMON DH, GOODSON NJ, KATZ JN, et al.: Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis. 2006;65:1608-12. [2] JAFRI K, BARTELS CM, SHIN D, GELFAND JM, OGDIE A: Incidence and management of cardiovascular risk factors in psoriatic arthritis and rheumatoid arthritis: A population-based study. Arthritis Care Res (Hoboken). 2017;69:51-7. [3] AN J, ALEMAO E, REYNOLDS K, et al.: Cardiovascular outcomes associated with lowering low-density lipoprotein cholesterol in rheumatoid arthritis and matched nonrheumatoid arthritis. J Rheumatol. 2016;43:1989-96. Acknowledgement: This project was sponsored by the grants from the National Natural Science Foundation of China (No. 81671610, 81471610, 81471611, 81801625) Disclosure of Interests: None declared