Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 11/10/2005
Publication Date: 3/6/2006
Citation: Schuschke, D.A., Williams, C., Kang, Y.J., Saari, J.T. 2006. Cu-repletion promotes angiogenesis in the Cu-deficient rat heart [abstract]. Journal of Federation of American Societies for Experimental Biology. 20(4):A553.
Technical Abstract: Heart hypertrophy is a common manifestation of dietary copper deficiency in experimental animals. Upon repletion of copper, the hypertrophy is quickly reversed. Knowing this, the aim of this study was to compare angiogenesis during the hypertrophy and reverse remodeling seen in copper deficiency/repletion. Male adult rats (225 g) were fed either a purified Cu-adequate diet (6 mg Cu/kg diet) or a Cu-deficient diet (0.3 mg Cu/kg diet) for 8 weeks. Cu-deficient animals were then replenished with Cu-adequate diet for 1, 2 or 4 weeks. Echocardiography and heart wt/body wt ratio were used to determine hypertrophy. Heart tissue samples were collected and stained with anti-Factor VIII to quantify angiogenesis. Vascular endothelial growth factor (VEGF) was assayed by Western blot. Cu-deficient hearts exhibited significant hypertrophy along with lower capillary density and reduced VEGF content. Cu-repletion caused coincident increases in VEGF and angiogenesis. With repletion, the hypertrophy indices returned to control values. These results demonstrate an inverse relationship between angiogenesis and heart hypertrophy. The findings suggest involvement of a VEGF-dependent mechanism in myocardial reverse remodeling during copper repletion. Supported by NIH grant DK055030.