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Osteopontin expression in cardiomyocytes induces dilated cardiomyopathy.
- Source :
-
Circulation. Heart failure [Circ Heart Fail] 2010 May; Vol. 3 (3), pp. 431-9. Date of Electronic Publication: 2010 Mar 03. - Publication Year :
- 2010
-
Abstract
- Background: Inflammatory processes play a critical role in myocarditis, dilated cardiomyopathy, and heart failure. The expression of the inflammatory chemokine osteopontin (OPN) is dramatically increased in cardiomyocytes and inflammatory cells during myocarditis and heart failure in human and animals. However, its role in the development of heart diseases is not known.<br />Methods and Results: To understand whether OPN is involved in cardiomyopathies, we generated a transgenic mouse (MHC-OPN) that specifically overexpresses OPN in cardiomyocytes with cardiac-specific promoter-directed OPN expression. Young MHC-OPN mice were phenotypically indistinguishable from their control littermates, but most of them died prematurely with a half-life of 12 weeks of age. Electrocardiography revealed conduction defects. Echocardiography showed left ventricular dilation and systolic dysfunction. Histological analysis revealed cardiomyocyte loss, severe fibrosis, and inflammatory cell infiltration. Most of these inflammatory cells were activated T cells with Th1 polarization and cytotoxic activity. Autoantibodies against OPN, cardiac myosin, or troponin I, were not found in the serum of MHC-OPN mice.<br />Conclusions: These data show that OPN expression in the heart induces in vivo T-cell recruitment and activation leading to chronic myocarditis, the consequence of which is myocyte destruction and hence, dilated cardiomyopathy. Thus, OPN might therefore constitute a potential therapeutic target to limit heart failure.
- Subjects :
- Animals
Cardiomyopathy, Dilated etiology
Disease Models, Animal
Fibrosis etiology
Fibrosis metabolism
Fibrosis pathology
Heart Failure etiology
Lymphocyte Activation
Mice
Mice, Transgenic
Myocarditis etiology
Myocarditis metabolism
Myocarditis pathology
Neutrophil Infiltration
Cardiomyopathy, Dilated metabolism
Cardiomyopathy, Dilated pathology
Heart Failure metabolism
Heart Failure pathology
Myocytes, Cardiac metabolism
Osteopontin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1941-3297
- Volume :
- 3
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Circulation. Heart failure
- Publication Type :
- Academic Journal
- Accession number :
- 20200330
- Full Text :
- https://doi.org/10.1161/CIRCHEARTFAILURE.109.898114