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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #243147
Title: Regression of Copper-Deficient Heart Hypertrophy: Reduction in the Size of Hypertrophic Cardiomyocytes

Author
item ZHOU, ZHANXIANG - University Of Louisville
item Johnson, William
item KANG, Y - University Of Louisville

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/6/2008
Publication Date: 8/1/2009
Citation: Zhou, Z., Johnson, W.T., Kang, Y.J. 2009. Regression of Copper-Deficient Heart Hypertrophy: Reduction in the Size of Hypertrophic Cardiomyocytes. Journal of Nutritional Biochemistry. 20(8):621-628.

Interpretive Summary: Experiments with laboratory animals have shown that low copper intake leads to heart enlargement. It also has been found the low copper intake by humans leads to heart arrhythmias and that the hearts of people who succumbed to heart disease often have lower than normal levels copper. The present study shows that copper deficiency leads to heart enlargement in mice by increasing the size of heart cells while at the same time reducing their number. Furthermore, treating the copper-deficient mice with adequate dietary copper led to the reversal of heart enlargement by reducing the size of the heart cells and increasing their number. The finding that adequate Cu intake could increase the number of heart cells is important because it indicates that copper may trigger damaged hearts to produce new cells to replace the defective ones. This finding has implications for human health because it suggests that dietary copper requirements for heart patients may be higher than the normal recommended daily intake.

Technical Abstract: Dietary copper deficiency causes cardiac hypertrophy and its transition to heart failure in a mouse model. Copper repletion results in a 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 copper deficient diet (0.3 mg Cu/kg) starting from day 3 post delivery and weanling pups were fed the same diet until copper repletion (6.0 mg Cu/kg) in the diet at 31 days of age. Heart samples were obtained at the end of copper deficient feeding or at 3, 7, 14 or 28 days after copper repletion. Copper deficiency resulted in increases in the size and reduction in the number of cardiomyocytes in the heart. Copper 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 underwent division upon copper repletion, as determined by a mitosis-specific marker phosphor-histone H3. Quantitative analysis.