Effect of antioxidants on atherosclerotic plaque formation in balloon-denuded and irradiated hypercholesterolemic rabbits.
The oxidative modification of low-density lipoprotein (LDL) hypothesis implies that antioxidants should be effective in suppressing atherosclerosis. This study is designed to test the potential of antioxidants to inhibit atherosclerotic plaque progression in balloon-denuded and irradiated hypercholesterolemic rabbits. Rabbits were fed with a 1% cholesterol diet supplemented with or without a mixture of antioxidants (vitamin E, vitamin C, selenium, zinc, copper, manganese, N-acetylcysteine, glutamine). At 7 days both iliac arteries were balloon denuded, and 4 weeks later, 1 iliac artery underwent endovascular irradiation (n=12), while the contralateral was sham treated (n=12). Four weeks after irradiation, animals were euthanized, and arteries were fixed and processed for histo- or immunohistochemistry for determining the plaque area, macrophage count, and oxidized LDL-positive areas. Plasma antioxidant levels were significantly higher in the animals fed with antioxidant diet. Plasma (thiobarbituric acid-reactive substances) and arterial tissue oxidized LDL (immunoreactive to specific oxidized LDL antibody) levels were significantly higher in the irradiated as compared with nonirradiated animals (0.69+/-0.09 and 31.05+/-4.21 versus 0.24+/-0.04 and 18.42+/-4.62, P<0.001 and 0.05), and antioxidants partially lowered the oxidized LDL levels (0.35+/-0.14 and 25.41+/-4.82, P<0.001 and 0.01). Plaque area in the irradiated animals was 175% greater than in nonirradiated animals (P<0.05). Antioxidant supplementation resulted in a 50% decrease in plaque area of both control and irradiated animals. Antioxidants reduced both the cholesterol-induced and radiation-enhanced circulating and tissue oxidized LDL levels, resulting in reduced plaque.
Leborgne
Laurent
L
Cardiovascular Research Institute, Washington Hospital Center, Washington, DC 20010, USA.
Pakala
Rajbabu
R
Dilcher
Christian
C
Hellinga
David
D
Seabron
Rufus
R
Tio
Fermin O
FO
Waksman
Ron
R
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D002404:Catheterization / Q000009:adverse effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D019587:Dietary Supplements; D004195:Disease Models, Animal; D018450:Disease Progression; D006937:Hypercholesterolemia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D007083:Iliac Artery / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D011817:Rabbits; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D002791:Cholesterol, Dietary; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde