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.
Lamb
David J
DJ
Centre for Clinical Science and Measurement, School of Biomedical and Life Sciences, University of Surrey, Surrey GU27XH, Guildford, UK
Avades
Tony Y
TY
Allen
Michael D
MD
Anwar
Khurshid
K
Kass
George E N
GE
Ferns
Gordon A A
GA
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