Creatine kinase knockout mice show left ventricular hypertrophy and dilatation, but unaltered remodeling post-myocardial infarction
Creatine kinase knockout mice show left ventricular hypertrophy and dilatation, but unaltered remodeling post-myocardial infarction
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DOI：
10.1016/j.cardiores.2004.10.006
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发表时间：
2005-02-01
影响因子：
10.8
通讯作者：
Neubauer, S
中科院分区：
文献类型：
--
作者：
Nahrendorf, M;Spindler, M;Neubauer, S
目的：肌酸激酶(CK)负责高能磷酸盐在可兴奋组织中的运输，在心肌能量平衡中起着核心作用。据报道，在缺乏各种CK同工酶的小鼠中，心肌能量学发生了显著的变化。方法：用心脏磁共振成像(MRI)检测CK缺陷小鼠(CK-KO)的左心室容量、射血分数和质量：野生型(WT)10只，线粒体CK-/-6只(Mito-CK-/-)，细胞质CK-KO(M-CK-/-)10只，混合型KO(M/Mito-CK-/-)10只。Mito-CK-/-组和M/Mito-CK-/-组有显著的左室扩张，左室舒张末期容量增加30%。与WT组相比，Mito-CK-/-组和M/Mito-CK-/-组小鼠的左心室重量分别增加了73%和%，但无明显增加(+33%；P=N.S.)在M-CK-/-。此外，心肌肥厚的标志物--β-MHC在所有CK缺乏的心脏中都有显著的重新表达。应用核磁共振技术观察7只WT和10只M/Mito-CK-/-小鼠心肌梗死后4周的左心室重构。左前降支结扎4周后(心肌梗死面积接近32%)，WT和M/Mito-CK-/-表现出相似程度的心功能障碍、扩张和肥厚。结论：Mito-CK-/-和M/Mito-CK-/-小鼠表现出明显的左室扩张和明显的左室肥厚，但心肌梗死后左室重构并未加重。心肌梗死消融可导致心脏发生实质性适应性变化。(C)2004年欧洲心脏病学会。爱思唯尔出版，版权所有。
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 similar to30% 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 reexpression 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 similar to32%), 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. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.