OP0161 Cardiac Magnetic Resonance Imaging of Lupus Nephritis-Induced Cardiovascular Disease Correlates with Myocarditis, Fibrosis, and Enhanced Pro-Inflammatory Cytokine Expression in A Mouse Model. (15th July 2016)

• Record Type: Journal Article
• Authors: Young, N.A.; Hampton, J.; Kalyanasundaram, A.; Bratasz, A.; Pyles, J.; Aqel, S.; Jarjour, W.; Ardoin, S.
• Is Part Of: Annals of the rheumatic diseases. Volume 75(2016)Supplement 2
• Page Start: 116
• Page End: 117
• Publication Date: 2016-07-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2016-eular.4827
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Epidemiological data shows a bimodal pattern of mortality in lupus. The most deadly complications are associated with systemic lupus erythematosus (SLE) disease activities, including kidney disease and infections, in the first 10 years; subsequently, the primary cause of morbidity and mortality is cardiovascular disease (CVD). Previously, we used cardiac magnetic resonance imaging (CMR) with quantitative T2 mapping in human SLE and observed enhanced T2 signals in active patients during flares, which suggested sub-clinical levels of cardiac inflammation. Objectives: Since patients may significantly benefit from non-invasive monitoring of CVD, we used CMR to examine the NZM2410 animal model of lupus nephritis (LN), which develops severe lupus-like glomerulonephritis at 22–40 weeks of age. Methods: Myocardial edema was measured with T2 CMR mapping on the BioSpec 94/30 microMRI imaging system. Mice were monitored for cardiac abnormalities and physiological cardiac function using a high-frequency ultrasound echocardiogram (EC). Blood urea nitrogen (BUN) levels were measured to assess kidney function and ELISA was performed on cardiac tissue homogenates and serum. Heart tissue was collected for H&E, immunhistochemistry, and Masson's trichrome staining to measure tissue fibrosis. Results: As NZM2410 mice aged, a significantly enhanced expression of IL-1β, IL-2, IL-6, IL-10, CXCL1, and TNF-α was detected in both the serum and cardiac tissue. CMR T2 mapping was performed at 20–25 weeks of age and EC was used to monitor for cardiac abnormalities. When ECs indicated increased left ventricular diameter and residual volumes as well as significantly decreased ejection fractions relative to baseline, CMR with T2 mapping was performed again. Despite BUN levels and weight measurements showing no signs of end-stage renal disease, T2 signals were elevated and the myocardium thickened significantly to produce a prominent left ventricular hypertrophy upon MRI analysis. In addition, expression of IL-10, IL-2, IL-6, CXCL1, and TNF-α was significantly up-regulated in the serum of these mice. Histopathological examination revealed robust infiltrates in cardiac tissue with significant fibrosis. While immunohistochemical staining showed little to no detection of B-cells, neutrophils, or macrophages, IL-17 and CD3+ T-cells were observed in cardiac infiltrates. Conclusions: Our results demonstrate that myocarditis is associated with pro-inflammatory cytokine expression and LN disease progression in NZM2410 mice prior to end-stage renal disease. Consequently, our data establish CMR as a novel non-invasive technique to explore the contribution of SLE-mediated inflammation on CVD and to develop therapeutic strategies to pharmacologically inhibit cardiac damage. Future work will identify biomarkers associated with cardiac damage and will further develop CMR with quantitative T2 mapping as a clinical tool to assess CVD in patients with SLE. References: Ardoin, S, et al. CMR with Quantitative T2 Mapping in Patients with Active SLE [abstract]. Arthritis Rheumatol. October 2014; 66, S10. DOI: 10.1002/art.38914 Acknowledgement: The Ohio State University Wexner Medical Center. Disclosure of Interest: None declared