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 mm(2), P<0.05) and this was accompanied by a significant increase in aortic copper content (4.0+/-0.8 vs. 1.8+/-0.2 microg/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.
Centre for Clinical Science and Measurement, School of Biomedical and Life Sciences, University of Surrey, Surrey GU27XH, Guildford, UK
David J
DJ
Lamb
Tony Y
TY
Avades
Michael D
MD
Allen
Khurshid
K
Anwar
George E N
GE
Kass
Gordon A A
GA
Ferns
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D017209:Apoptosis / Q000502:physiology*; D001161:Arteriosclerosis / Q000473:pathology* / Q000628:therapy; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003300:Copper / Q000494:pharmacology*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D011336:Probability; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D017539:Tunica Intima / Q000473:pathology*
D002791:Cholesterol, Dietary; D003300:Copper