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United States Department of Agriculture

Agricultural Research Service

Title: Regression of Dietary Copper Restriction-Induced Cardiomyopathy by Copper Refeeding

Authors
item Elsherif, Laila - UNIV OF LOUISVILLE
item Wang, Lipeng - UNIV OF LOUISVILLE
item Liang, Youchun - UNIV OF LOUISVILLE
item Saari, Jack
item Kang, Y - UNIV OF LOUISVILLE

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: December 1, 2003
Publication Date: March 24, 2004
Citation: Elsherif, L., Wang, L., Liang, Y., Saari, J.T., Kang, Y.J. 2004. Regression of dietary copper restriction-induced cardiomyopathy by copper refeeding [abstract]. The Federation of American Societies for Experimental Biology Journal. 18:A915.

Interpretive Summary: Dietary copper (Cu) restriction leads to cardiac hypertrophy in various animal models. We have shown that heart failure develops after hypertrophy in mice fed copper deficient (CuD) diet. The present study was undertaken to determine whether CuD-induced cardiac hypertrophy is reversible upon copper refeeding (CuR). Dams of FVB mice were fed CuD (0.3 ppm Cu) diet starting from the third day post delivery and the weanling pups were fed the same diet until CuR with 6.0 ppm Cu in the diet at 4 or 5 wks of age. CuR at 4 wks of age prevented the body weight loss and at 5 wks of age resulted in regain of the lost weight caused by CuD. A significant regression of CuD-induced cardiac hypertrophy was observed in the CuR mice. Histopathological examination revealed that CuR eliminated CuD-caused myocardial damage. 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 relaxation time were completely recovered in the CuR mice. Furthermore, the CuD-blunted myocardial response to beta-adrenergic stimulation was also restored in the CuR mice. Real-time RT-PCR analysis of mRNA of contractile and Ca**2+-cycling proteins showed beneficial alterations up CuR. This study thus demonstrates that CuD-induced cardiomyopathy is reversible upon reintroduction of Cu in the diet.

Technical Abstract: Dietary copper (Cu) restriction leads to cardiac hypertrophy in various animal models. We have shown that heart failure develops after hypertrophy in mice fed copper deficient (CuD) diet. The present study was undertaken to determine whether CuD-induced cardiac hypertrophy is reversible upon copper refeeding (CuR). Dams of FVB mice were fed CuD (0.3 ppm Cu) diet starting from the third day post delivery and the weanling pups were fed the same diet until CuR with 6.0 ppm Cu in the diet at 4 or 5 wks of age. CuR at 4 wks of age prevented the body weight loss and at 5 wks of age resulted in regain of the lost weight caused by CuD. A significant regression of CuD-induced cardiac hypertrophy was observed in the CuR mice. Histopathological examination revealed that CuR eliminated CuD-caused myocardial damage. 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 relaxation time were completely recovered in the CuR mice. Furthermore, the CuD-blunted myocardial response to beta-adrenergic stimulation was also restored in the CuR mice. Real-time RT-PCR analysis of mRNA of contractile and Ca**2+-cycling proteins showed beneficial alterations up CuR. This study thus demonstrates that CuD-induced cardiomyopathy is reversible upon reintroduction of Cu in the diet.

Last Modified: 11/27/2014
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