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FTY720 (Gilenya) treatment prevents spontaneous autoimmune myocarditis and dilated cardiomyopathy in transgenic HLA-DQ8-BALB/c mice
- Source :
- Cardiovascular Pathology. 25:353-361
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Although dilated cardiomyopathy (DCM) is often caused by viral infections, it frequently involves autoimmune mechanisms associated with particular HLA-DR and DQ alleles. Our homozygous HLA-DQ8Ab(0) transgenic mice in the BALB/c background (HLA-DQ8(BALB/c)-Tg) developed early and progressive fatal heart failure from 4 to 5 weeks of age. Clinical signs of the disease included cyanotic eyes, tachycardia with dyspnea (from pale to cyanotic limbs), and terminal whole body edema. Sick mice had extremely dilated hearts, enlarged liver and spleen, and pleural/peritoneal effusion. Histology of the heart showed extensive heart muscle destruction with signs of fibrosis. The autoimmune nature of the disease was shown by high titers of antimyosin antibodies in the sera and IgG deposits in sick heart muscles, as well as focal neutrophil, T cell, and macrophage infiltration of the heart muscle. The sera of the sick mice showed a granular staining pattern on sections of healthy heart muscle. Quantitative analyses of DCM-specific gene expression studies revealed that sets of genes are involved in inflammation, hypoxia, and fibrosis. Treatment with FTY720 (Fingolimod/Gilenya) protected animals from the development of cardiomyopathy. HLA-DQ8(BALB/c)-Tg mice represent a spontaneous autoimmune myocarditis model that may provide a useful tool for studying the autoimmune mechanism of DCM and testing immunosuppressive drugs.
- Subjects :
- Cardiomyopathy, Dilated
0301 basic medicine
Pathology
medicine.medical_specialty
Blotting, Western
Cardiomyopathy
Mice, Transgenic
Spleen
Inflammation
030204 cardiovascular system & hematology
Autoantigens
Article
Autoimmune Diseases
Pathology and Forensic Medicine
BALB/c
Mice
03 medical and health sciences
0302 clinical medicine
Mice, Inbred NOD
Fibrosis
HLA-DQ Antigens
Edema
medicine
Animals
Humans
Autoantibodies
Mice, Inbred BALB C
Microscopy, Confocal
biology
Fingolimod Hydrochloride
business.industry
Heart
Dilated cardiomyopathy
General Medicine
biology.organism_classification
medicine.disease
Immunohistochemistry
Mice, Inbred C57BL
Disease Models, Animal
Myocarditis
030104 developmental biology
medicine.anatomical_structure
Heart failure
Immunology
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Cardiac Myosins
Immunosuppressive Agents
Subjects
Details
- ISSN :
- 10548807
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Cardiovascular Pathology
- Accession number :
- edsair.doi.dedup.....760afa177eecb40581875fa894164dd3