Dietary Cholesterol Supplements Disturb Copper Homeostasis in Multiple Organs in Rabbits: Aorta Copper Concentrations Negatively Correlate with the Severity of Atherosclerotic Lesions.

Dietary cholesterol causes atherosclerosis along with a reduction of copper concentrations in the atherosclerosis wall. This study was to determine the relationship between aorta copper concentrations and the severity of atherosclerotic lesions as well as copper homeostasis in multiple organs in cholesterol-fed rabbits. Male New Zealand white rabbits, 10-week-old and averaged 2.0 kg, were fed a diet containing 1% (w/w) cholesterol or the same diet without cholesterol as controls. Twelve weeks after the feeding, aortic atherosclerotic lesions, serum cholesterol, and multiple organ copper concentrations were measured. Compared to controls, rabbits fed cholesterol-supplemented diet displayed higher serum cholesterol levels and developed atherosclerosis. Copper concentrations in the cholesterol-fed rabbits were increased in the serum and kidney but decreased in the atherosclerosis wall and multiple organs, including heart, liver, spleen, and lung. Furthermore, aorta copper concentrations negatively correlated, respectively, with the severity of the atherosclerotic lesion (r = - 0.64, p = 0.01), the microscope atherosclerotic lesion area (r = - 0.60, p = 0.02), and the stenosis of the lumen (r = - 0.54, p = 0.04). Dietary cholesterol not only causes atherosclerosis but also disturbs copper homeostasis in multiple organ systems. The negative correlation between aorta copper concentrations and the severity of atherosclerotic lesions suggests a vicious cycle between copper reduction and the pathogenesis of atherosclerosis. These changes in copper homeostasis would be additive to atherosclerosis as a risk factor for cardiovascular disease in humans.