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.

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.

• Authors: Matthias Nahrendorf, Matthias Spindler, Kai Hu, Lisa Bauer, Oliver Ritter, Peter Nordbeck, Thomas Quaschning, Karl-Heinz Hiller, Julie Wallis, Georg Ertl, Wolfgang R Bauer, Stefan Neubauer
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 65 Issue 2 Pg. 419-27 (Feb 01 2005) ISSN: 0008-6363 [Print] England
• PMID: 15639481 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• Creatine Kinase

Topics

• Animals
• Cardiomyopathy, Dilated (genetics, pathology)
• Creatine Kinase (genetics)
• Cytosol (enzymology)
• Female
• Hypertrophy, Left Ventricular (genetics, pathology)
• Isoenzymes (genetics)
• Magnetic Resonance Imaging
• Male
• Mice
• Mice, Knockout
• Mitochondria, Heart (enzymology)
• Myocardium (enzymology, pathology)