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Research Project: Nutrition, Aging, Immune Function, and Inflammatory Response in Health and Disease

Location: Human Nutrition Research Center on Aging

Title: Vitamin E Supplementation Suppresses Macrophage Accumulation and Endothelial Cell Expression of Adhesion Molecules in the Aorta of Hypercholesterolemic Rabbits

Authors
item Koga, Takuro - KIKKOMAN COMP, CHIBA, JPN
item Kwan, Paul - TUFTS UNIVERSITY
item Zubik, Ligia - TUFTS-HNRCA
item Ameho, Clement - TUFTS-HNRCA
item Smith, Donald - TUFTS-HNRCA
item Meydani, Mohsen - TUFTS-HNRCA

Submitted to: Atherosclerosis
Publication Acceptance Date: May 17, 2004
Publication Date: September 21, 2004
Publisher's URL: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T12-4DCDH8H-2&_coverDate=10%2F01%2F2004&_
Citation: Koga, T., Kwan, P., Zubik, L., Ameho, C., Smith, D., Meydani, M. 2004. Vitamin E Supplementation Suppresses Macrophage Accumulation And Endothelial Cell Expression Of Adhesion Molecules In The Aorta Of Hypercholesterolemic Rabbits. Atherosclerosis. 176(2):265-272.

Interpretive Summary: High levels of cholesterol is one of the most important risk factors for atherosclerosis and vascular disease. Conflicting results regarding the effects of vitamin E supplementation on atherosclerosis progression and cardiovascular disease (CVD) have been reported from randomized controlled trials. However, compelling evidence from experimental in vitro studies and in vivo studies as well as from epidemiological studies support the potential role of dietary antioxidants like vitamin E in reducing the risk of CVD. In this study, before inducing of high cholesterol levels through diet, rabbits were fed either a control diet or a diet supplemented with vitamin E for 4 weeks. Rabbits that consumed either the control or vitamin E supplemented diet had similar daily food intakes and growth rate as determined by body weight. Concentration of plasma cholesterol was the same for both groups of rabbits up to the 4th week and significantly increased after introducing the atherogenic diet. In vitamin E supplemented rabbits, the plasma concentration of vitamin E (alpha-tocopherol) was significantly higher than control rabbits at 2 and 4 weeks. Following the introduction of the atherogenic diet after the 4th week, because of the increase in plasma cholesterol levels, the plasma level of vitamin E was further increased, and it was significantly higher when the levels were adjusted per mg of plasma cholesterol. Vitamin E supplementation also increased the levels of vitamin E in the aorta. However, the levels of cholesterol in the aortic tissue were the same in both groups. These results support the concept that vitamin E may suppress the development of aortic lesions in a rabbit model of atherosclerosis and lead us to better understanding this mechanism in preventing atherosclerosis in humans by way of Vitamin E supplementation.

Technical Abstract: Suppression of cell adhesion molecule expression and macrophage accumulation by the endothelium is believed to play an important role in preventing atherosclerosis. We have shown that in vitro supplementation of human aortic endothelial cells with vitamin E dose-dependently reduced expression of adhesion molecules and monocyte adhesion. Here, we report the in vivo down-regulation of endothelial cell adhesion molecules expression and macrophage accumulation in the aortas of hypercholesterolemic rabbits supplemented with vitamin E. To this end, New Zealand White rabbits were fed a semi-purified diet containing 30 (control) or 1000 IU/kg vitamin E. After 4 weeks, both groups' diets were switched to an atherogenic diet (0.3 % cholesterol, 9 % hydrogenated coconut oil, and 1 % corn oil) containing the respective levels of vitamin E and fed for 2, 4, and 6 weeks. Vitamin E supplemented rabbits had significantly higher levels of vitamin E in their plasma and aortas. At 6 weeks on atherogenic diet treatment, a trend (p=0.08) toward a lower score of ICAM-1 expression by endothelial cells was observed in the aorta of vitamin E treated rabbits compared to the control. However, a decrease in the score of VCAM-1 expression by endothelial cells in vitamin E treated rabbits did not reach to a statistical significance. At 4 and 6 weeks on atherogenic diet, vitamin E supplementation also significantly (p=0.003) inhibited the accumulation of macrophages in the aorta. These results support the concept that down-regulation of adhesion molecule expression and suppression of monocyte/macrophage activation by vitamin E in vivo is one of the potential mechanisms by which vitamin E may suppress the development of aortic lesions in a rabbit model of atherosclerosis.

 
Project Team
Wilhelm, Kathi
Simin Meydani - Lab Chief 617-556-3312

Publications

Related National Programs
  Human Nutrition (107)

 
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