Dietary copper supplementation reduces atherosclerosis in the cholesterol-fed rabbit

There has been considerable debate about how copper status may affect the b iochemical and cellular processes associated with atherogenesis. In the pre sent study we have attempted to address this issue directly by investigatin g the effects of dietary copper supplementation on processes likely to cont ribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Age matched rabbits (n = 16) were fed a 0.25-1% cholesterol diet to maintain plasma cholesterol concentrations at approximately 30 mmol/l. Eig ht of these animals also received 0.2% copper acetate. Control animals (n = 8) received rabbit chow without supplements. After 13 weeks on the experim ental diets the animals were killed. Integrated cholesterol levels were sim ilar for the cholesterol-fed animals (31.1 +/- 2.5 vs. 29.9 +/- 1.9 mmol/l weeks; P > 0.05). Although integrated plasma copper levels were higher in t he animals receiving the copper supplements, these did not differ significa ntly (19.0 +/- 4.8 vs. 15.1 +/- 2.9 mu mol/l weeks; P > 0.05), Tissue conce ntrations of copper were higher in the copper fed animals compared to those on cholesterol alone in aortic (4.0 +/- 0.75 vs, 1.8 +/- 0.2 mu g/g wet ti ssue; P < 0.05), carotid artery (11.4 +/- 3.5 vs. 4.9 +/- 0.9 mu g/g wet ti ssue; P < 0.05),and hepatic (332.5 +/- 28.6 vs. 3.3 +/- 1.1 mu g/g wet tiss ue; P < 0.0001) samples. The concentration of copper within the carotid art ery was also significantly higher than that within the aorta (7.5 +/- 1.8 v s. 2.4 +/- 0.4 mu g/g wet tissue; P < 0.05). In animals fed a normal rabbit chow aortic, carotid and hepatic copper concentrations were 3.7 +/- 0.8, 9 .4 +/- 3.4, and 5.0 +/- 1.6 mu g/g, respectively. These values did not diff er significantly from the cholesterol-fed animals (P > 0.05). Plasma concen trations of caeruloplasmin, the major copper carrying protein, were estimat ed as plasma ferroxidase activity and were similar for the groups (P > 0.05 ), as were aortic superoxide dismutase activity levels (P > 0.05). Copper s upplementation was associated with increased mononuclear cell adhesion to t he endothelium of the carotid endothelium, with 2.6 +/- 0.3 adherent monocy tes/1000 endothelial cells in the cholesterol plus copper-fed animals compa red to 1.3 +/- 0.3 in the cholesterol-fed group (P = 0.0.0006), and 0.1 +/- 0.1 in the control animals (P < 0.002). This may reflect the higher concen trations of copper found within the carotid artery. Histology of the thorac ic aorta at the level of the third and sixth intercostal arteries, showed t hat copper supplementation was associated with significantly smaller intima l lesions (P < 0.05 and P < 0.01, respectively). These data suggest that co pper supplements possibly inhibit the progression of atherogenesis. (C) 199 9 Elsevier Science Ireland Ltd. All rights reserved.