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

Authors
  • Young, Nicholas A1
  • Jablonski, Kyle1
  • Schwarz, Emmy1
  • Okafor, Ifeoma1
  • Hampton, Jeffrey1
  • Valiente, Giancarlo R1
  • Henry, Caitlin1
  • Harb, Peter1
  • Barger, Jessica2
  • Bratasz, Anna2
  • Kalyanasundaram, Anuradha3
  • Ardoin, Stacy P4
  • Jarjour, Wael N1
  • 1 Department of Internal Medicine, Division of Immunology and Rheumatology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • 2 Small Animal Imaging Core, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • 3 Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • 4 Pediatric & Adult Rheumatology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Type
Published Article
Journal
Lupus
Publisher
SAGE Publications
Publication Date
Nov 01, 2020
Volume
29
Issue
13
Pages
1790–1799
Identifiers
DOI: 10.1177/0961203320948959
PMID: 33045900
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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). 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. 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. 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.

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