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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 #161756
Title: REGRESSION OF DIETARY COPPER RESTRICTION-INDUCED CARDIOMYOPATHY BY COPPER REPLETION IN MICE

Author
item EL-SHERIF, LAILA - UNIV OF LOUISVILLE
item WANG, LIPENG - UNIV OF LOUISVILLE
item Saari, Jack
item KANG, Y - UNIV OF LOUISVILLE

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/13/2004
Publication Date: 4/1/2004
Citation: Elsherif, L., Wang, L., Saari, J.T., Kang, Y.J. 2004. Regression of dietary copper restriction-induced cardiomyopathy by copper repletion in mice. Journal of Nutrition. 134:855-860.

Interpretive Summary: Dietary copper deficiency leads to a variety of detrimental changes in the heart, including structural, molecular and functional changes that are suggestive of heart failure. The purpose of this study was to determine whether repletion of copper in the diets of mice fed severely copper-deficient diets from just after birth could ameliorate these changes. We found that copper repletion after two or four weeks of severe deficiency prevented or ameliorated the weight loss of copper deficiency, the detrimental structural changes within heart cells and the impaired contraction and relaxation of the heart, including contractile responses to a stimulating agent that mimics adrenaline. This indicates that replenishment of copper can avert symptoms of heart failure in severely copper-deficient animals.

Technical Abstract: Dietary copper deficiency (CuD) leads to cardiac hypertrophy in various animal models. We have recently shown that heart failure develops after hypertrophy in FVB mice fed copper deficient diet. The present study was undertaken to determine whether CuD-induced cardiac failure is reversible upon copper repletion (CuR). Dams of FVB mice were fed copper deficient diet (0.3 mg/kg) starting from the d 3 post delivery and the weanling pups were fed the same diet until CuR with 6.0 mg/kg Cu in the diet at 4 or 5 wk of age. CuR at 4 wk of age prevented the body weight loss and at 5 wk of age resulted in regain of the lost weight caused by CuD. A significant regression of CuD-induced cardiac hypertrophy was observed in the copper repleted mice. Histopathological examination revealed that CuR eliminated CuD-caused lipid deposition in the myocardium and electron microscopy demonstrated that CuD-induced ultrastructural changes such as mitochondrial swelling and organelles structural disarray were also reversed in the copper repleted mice. Hemodynamic analysis showed that the CuD-depressed systolic and diastolic parameters such as the maximal rate of left ventricular pressure rise (+dP/dt) and decline (-dP/dt) and the contraction and relaxation times were completely recovered in the copper repleted mice. Furthermore, the CuD-blunted myocardial responses to beta-adrenergic agonist, isoproterenol, were also restored in the copper repleted mice. This study thus demonstrates for the first time that CuR results in regression of heart failure induced by CuD as demonstrated by the reversal of depressed cardiac hemodynamic and contractile function and the restored responsiveness to beta-adrenergic stimulation.