title: Creatine kinase knockout mice show left ventricular hypertrophy and dilatation, but unaltered remodeling post-myocardial infarction.
abstract: OBJECTIVE
  Creatine kinase (CK) is responsible for the transport of high-energy phosphates in excitable tissue and is of central importance in myocardial energy homeostasis. Significant changes in myocardial energetics have been reported in mice lacking the various CK isoenzymes. Our hypothesis was that ablation of CK isoenzymes leads to cardiac hypertrophy, impaired function, and aggravation of left ventricular remodeling post-myocardial infarction.
  
  
  METHODS
  CK-deficient mice (CK KO) were examined by cardiac magnetic resonance imaging (MRI) to determine left ventricular volumes, ejection fraction, and mass: ten wild-type (WT), 6 mitochondrial CK KO (Mito-CK-/-), 10 cytosolic CK KO (M-CK-/-), and 10 mice with combined KO (M/Mito-CK-/-).
  
  
  RESULTS
  While ejection fraction was similar in all groups, there was significant LV dilatation with a approximately 30% increase in LV end-diastolic volumes in Mito-CK-/- and in M/Mito-CK-/-. Compared to WT, there was a striking 73% and 64% increase of LV mass in Mito-CK-/- and in M/Mito-CK-/- mice, respectively, but no significant increase of LV mass (+33%; p=n.s.) in M-CK-/-. Furthermore, significant re-expression of beta-MHC, a marker of myocardial hypertrophy, was found in all CK-deficient hearts. LV remodeling was investigated by MRI in hearts of 7 WT and 10 M/Mito-CK-/- mice 4 weeks postmyocardial infarction (MI). Four weeks post-LAD ligation (MI size approximately 32%), WT and M/Mito-CK-/- showed a similar degree of cardiac dysfunction, dilatation, and hypertrophy.
  
  
  CONCLUSIONS
  Mito-CK-/- and M/Mito-CK-/- mice show significant LV dilatation and marked LV hypertrophy, but LV remodeling post-MI is not aggravated. CK ablation leads to substantial adaptational changes in heart.
authors.affiliation: Medizinische Universitätsklinik Würzburg, Universität Würzburg, Josef Schneider Str. 2, 97080 Würzburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Matthias
authors.initials: M
authors.lastname: Spindler
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Lisa
authors.initials: L
authors.lastname: Bauer
authors.forename: Oliver
authors.initials: O
authors.lastname: Ritter
authors.forename: Peter
authors.initials: P
authors.lastname: Nordbeck
authors.forename: Thomas
authors.initials: T
authors.lastname: Quaschning
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Hiller
authors.forename: Julie
authors.initials: J
authors.lastname: Wallis
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Bauer
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000473:pathology; D003402:Creatine Kinase / Q000235:genetics*; D003600:Cytosol / Q000201:enzymology; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000235:genetics* / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology
chemical_list: D007527:Isoenzymes; D003402:Creatine Kinase