Regression of copper-deficient heart hypertrophy: reduction in the size of hypertrophic cardiomyocytes.
Regression of copper-deficient heart hypertrophy: reduction in the size of hypertrophic cardiomyocytes.
复制标题
缺铜心脏肥大的消退：肥大心肌细胞大小的减少。
DOI：
10.1016/j.jnutbio.2008.06.007
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kang,YJames
中科院分区：
文献类型：
--
作者：
Zhou,Zhanxiang;Johnson,WThomas;Kang,YJames
在小鼠模型中，膳食铜（Cu）缺乏导致心脏肥大及其向心力衰竭的转变。铜补充导致心脏肥大的快速消退和心力衰竭的预防。本研究旨在了解肥厚心脏在退行性变过程中心肌细胞的动态变化。从分娩后第3天开始，用铜缺乏（CuD）饲料（0.3 mg Cu/kg）喂养FVB小鼠的母鼠，用相同的饲料喂养断奶幼仔，直至31日龄时饲料中的铜补充（6.0 mg Cu/kg）。在CuD喂养结束时或在Cu补充后3、7、14或28天获得心脏样品。铜缺乏导致心脏中心肌细胞的大小增加和数量减少。铜的补充导致萎缩的心肌细胞的大小和正常化的心肌细胞的总数。尽管细胞大小的直接减小是心脏肥大消退的重要原因，但通过心肌细胞特异性α-肌节肌动蛋白染色细胞中的Ki-67染色确定，一些肥大的心肌细胞在铜补充后重新进入细胞周期，并通过有丝分裂特异性标记物磷酸化组蛋白3确定进行分裂。定量分析表明，肥大心肌细胞的复制约占再生心肌总有丝分裂的三分之一。这项研究表明，直接减少一些肥大的心肌细胞的大小和复制的其他肥大的心肌细胞与减少的大小作出了显着的贡献，以回归CuD心脏肥大，导致正常化的大小和数量的心肌细胞在心脏。
Dietary copper (Cu) deficiency causes cardiac hypertrophy and its transition to heart failure in a mouse model. Cu repletion results in rapid regression of cardiac hypertrophy and prevention of heart failure. The present study was undertaken to understand dynamic changes of cardiomyocytes in the hypertrophic heart during the regression. Dams of FVB mice were fed with a Cu-deficient (CuD) diet (0.3 mg Cu/kg) starting on Day 3 post-delivery, and weanling pups were fed with the same diet until Cu repletion (6.0 mg Cu/kg) in the diet at 31 days of age. Heart samples were obtained at the end of CuD feeding or at 3, 7, 14 or 28 days after Cu repletion. Cu deficiency resulted in increases in the size and reduction in the number of cardiomyocytes in the heart. Cu repletion led to regression in the size of hypertrophic cardiomyocytes and normalization of the total number of cardiomyocytes. Although a direct reduction in the cell size would be significantly responsible for the regression of heart hypertrophy, some hypertrophied cardiomyocytes upon Cu repletion reentered the cell cycle as determined by Ki-67 staining in the cardiomyocyte-specific α-sarcomeric actin-stained cells and underwent division as determined by a mitosis-specific marker, phospho-histone 3. Quantitative analysis indicated that the replication of hypertrophic cardiomyocytes made a contribution of about one-third to the total mitosis of the regenerated myocardium. This study suggests that a direct reduction in the size of some hypertrophied cardiomyocytes and a replication of other hypertrophied cardiomyocytes with reduced size make a significant contribution to the regression of CuD heart hypertrophy, leading to normalization of the size and the number of cardiomyocytes in the heart.