Effect of dietary copper supplementation on cell composition and apoptosis in atherosclerotic lesions of cholesterol-fed rabbits

We have previously shown that dietary copper supplementation modulates the formation of atherosclerotic lesions in the cholesterol-fed rabbit. In the present study, we have investigated the effects of copper supplementation on the cellular composition and characteristics of atherosclerotic lesions in cholesterol-fed NZW rabbits. Rabbits received a 1% cholesterol diet with or without 0.02% copper acetate (containing 12 and 0.3 mg copper per 100 g diet, respectively) for 12 weeks. The tunica intima was significantly smaller in the animals receiving copper supplements (0.016±0.005 vs. 0.068±0.019 mm2, P<0.05) and this was accompanied by a significant increase in aortic copper content (4.0±0.8 vs. 1.8±0.2 μg/g tissue, P<0.05). The percentage area staining for smooth muscle cells (HHF-35 positive) was significantly lower in the intima of animals receiving copper supplements (7.13±1.02 vs. 9.72±0.82%, P<0.05). However, there were no significant differences in area staining for macrophages (RAM-11 positive) between groups (22.6±7.9 vs. 23.3±4.9%). There were also significantly fewer apoptotic cells (0.96±0.33 vs. 2.54±0.56%, P<0.005) in the aortic intima from animals supplemented with copper, but no difference in the number of proliferating cells. However, there was a reduction in intimal collagen staining (Sirius red positivity) in the animals receiving a copper supplement. Taken together, these data show that dietary copper can significantly affect the composition and progression of atherosclerotic lesions.