Copyright © 2004, European Society of Cardiology
Creatine kinase knockout mice show left ventricular hypertrophy and dilatation, but unaltered remodeling post-myocardial infarction
aMedizinische Universitätsklinik Würzburg, Universität Würzburg, Josef Schneider Str. 2, 97080 Würzburg, Germany
bPhysikalisches Institut (EP5), Universität Würzburg, Am Hubland, 97074 Würzburg, Germany
cDepartment of Cardiovascular Medicine, John Radcliffe Hospital, Oxford University, UK
* Corresponding author. Tel.: +49 931 2010; fax: +49 931 20136664. Email address: Spindler_M{at}medizin.uni-wuerzburg.de
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 
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 β-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 32%), WT and M/Mito-CK–/– showed a similar degree of cardiac dysfunction, dilatation, and hypertrophy.
Conclusion: 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.
KEYWORDS Energy metabolism; Hypertrophy; NMR; Remodeling; Transgenic animal models
1 Joint first authors who have contributed equally to this work.
Time for primary review 24 days
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