title: Osteopontin expression in cardiomyocytes induces dilated cardiomyopathy.
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.
  
  
  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.
  
  
  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.
authors.affiliation: INSERM U828, Ave. du Haut Lévêque, Pessac, France.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Renault
authors.forename: Fanny
authors.initials: F
authors.lastname: Robbesyn
authors.forename: Patricia
authors.initials: P
authors.lastname: Réant
authors.forename: Victorine
authors.initials: V
authors.lastname: Douin
authors.forename: Danièle
authors.initials: D
authors.lastname: Daret
authors.forename: Cécile
authors.initials: C
authors.lastname: Allières
authors.forename: Isabelle
authors.initials: I
authors.lastname: Belloc
authors.forename: Thierry
authors.initials: T
authors.lastname: Couffinhal
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Arnal
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.forename: Claude
authors.initials: C
authors.lastname: Desgranges
authors.forename: Pierre
authors.initials: P
authors.lastname: Dos Santos
authors.forename: Flavien
authors.initials: F
authors.lastname: Charpentier
authors.forename: Alain-Pierre
authors.initials: AP
authors.lastname: Gadeau
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D009205:Myocarditis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D020556:Neutrophil Infiltration; D053495:Osteopontin / Q000378:metabolism*
chemical_list: D053495:Osteopontin