title: Cardiotin localization in mitochondria of cardiomyocytes in vivo and in vitro and its down-regulation during dedifferentiation.
abstract: BACKGROUND
  Cardiotin expression is observed in adult cardiac tissue. In the present study, we provide evidence for the specific localization of cardiotin in cardiac mitochondria and for its down-regulation during adaptive remodeling (dedifferentiation) of cardiomyocytes.
  
  
  METHODS
  Immunocytochemistry was used to study cardiotin localization in adult rabbit papillary muscle, in late-stage embryonic rabbit left ventricular tissue, and in left ventricle samples of rabbits suffering from pressure and volume overload. Western blot analysis of cardiotin was performed in purified pig heart mitochondrial fractions. Cardiotin expression was monitored in vitro in isolated adult rat and rabbit left ventricular cardiomyocytes.
  
  
  RESULTS
  Western blot analysis revealed the presence of cardiotin in the mitochondrial fractions of pig heart. Immunoelectron microscopy confirmed the presence of cardiotin in cardiac mitochondria of normal adult rabbits both in vivo and in vitro. Quantification of the localization of immunogold particles suggests an association of cardiotin with the mitochondrial inner membrane. Cardiotin expression is initiated in late-stage embryonic rabbit heart, whereas in adult ventricular tissue cardiotin clearly stained longitudinal arrays of mitochondria. Pressure- and volume-overloaded myocardium showed a reduction in cardiotin expression in dispersed local myocardial areas. Cell cultures of adult cardiomyocytes showed a gradual loss in cardiotin expression in parallel with a sarcomeric remodeling.
  
  
  CONCLUSIONS
  Our results demonstrate the specific localization of cardiotin in adult cardiomyocyte mitochondria and propose its use as an early marker for cardiomyocyte adaptive remodeling and dedifferentiation.
authors.affiliation: Department of Molecular Cell Biology, School for Cardiovascular Diseases (CARIM), University of Maastricht, Maastricht, The Netherlands. r.driesen@molcelb.unimaas.nl
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Driesen
authors.forename: Fons K
authors.initials: FK
authors.lastname: Verheyen
authors.forename: Gert
authors.initials: G
authors.lastname: Schaart
authors.forename: Ann
authors.initials: A
authors.lastname: de Mazière
authors.forename: Christoph
authors.initials: C
authors.lastname: Viebahn
authors.forename: Frits W
authors.initials: FW
authors.lastname: Prinzen
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Lenders
authors.forename: Wiel
authors.initials: W
authors.lastname: Debie
authors.forename: Andreas
authors.initials: A
authors.lastname: Totzeck
authors.forename: Marcel
authors.initials: M
authors.lastname: Borgers
authors.forename: Frans C S
authors.initials: FC
authors.lastname: Ramaekers
mesh_terms: D000185:Actinin / Q000378:metabolism*; D000818:Animals; D001022:Aortic Valve Insufficiency / Q000378:metabolism* / Q000473:pathology; D054337:Cell Dedifferentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006321:Heart / Q000196:embryology; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009928:Organ Specificity; D010210:Papillary Muscles / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D011817:Rabbits; D051381:Rats; D013552:Swine
chemical_list: C104594:cardiotin; D000185:Actinin