Pathological manifestation of autoimmune myocarditis is detected prior to glomerulonephritis in a murine model of lupus nephritis.

Abstract:

OBJECTIVE:Since enhanced cardiac magnetic resonance imaging (cMRI) signals have been associated with lupus disease activity in humans prior to renal failure and novel, cardiac-focused therapeutic strategies could be investigated with an associated animal model, autoimmune myocarditis was characterized in murine lupus nephritis (NZM2410). METHODS:Weekly blood urea nitrogen (BUN) levels and weights were recorded. Cardiac function was assessed by echocardiogram. Myocardial edema was measured with quantitative T2 cMRI mapping. Endpoint serum and cardiac tissue were collected for histopathological analysis and cytokine measurements. RESULTS:Despite showing no signs of significant renal disease, mice displayed evidence of myocarditis and fibrosis histologically at 30-35 weeks. Moreover, T2 cMRI mapping displayed robust signals and analysis of sagittal heart sections showed significant myocardium thickening. Cytokine expression levels of IL-2, IL-10, TNF-α, CXCL1, and IL-6 were significantly enhanced in serum. Echocardiograms demonstrated significantly increased ventricular diameters and reduced ejection fractions, while immunohistochemical staining identified CD4+ and CD8+ T cells, and IL-17 in cardiac infiltrates. Human lupus cardiac tissue showed similar histopathology with enhanced infiltrates by H&E, fibrosis, and CD4+ detection. CONCLUSIONS:Histopathology, functional abnormalities, and enhanced cMRI signals indicative of myocarditis are detected in NZM2410 mice without glomerulonephritis, which supports the primary pathological role of autoimmune-mediated, cardiac-targeted inflammation in lupus.

journal_name

Lupus

journal_title

Lupus

authors

Young NA,Jablonski K,Schwarz E,Okafor I,Hampton J,Valiente GR,Henry C,Harb P,Barger J,Bratasz A,Kalyanasundaram A,Ardoin SP,Jarjour WN

doi

10.1177/0961203320948959

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

1790-1799

issue

13

eissn

0961-2033

issn

1477-0962

journal_volume

29

pub_type

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