Vitamin E supplementation suppresses macrophage accumulation and endothelial cell expression of adhesion molecules in the aorta of hypercholesterolemic rabbits.
Suppression of cell adhesion molecule expression and macrophage accumulation by the endothelium is believed to play an important role in preventing the development of atherosclerosis. Earlier, 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. Frozen aorta sections were fixed and stained by an avidin-biotin complex method using Rb2/3 and Rb1/9 monoclonal antibodies against rabbit ICAM-1 and VCAM-1, respectively, and with RAM-11 for macrophage and von Willebrand factor for endothelial cells, followed by staining with secondary antibodies and counterstaining and evaluation under the microscope. 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.
Koga
Takuro
T
Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
Kwan
Paul
P
Zubik
Ligia
L
Ameho
Clement
C
Smith
Donald
D
Meydani
Mohsen
M
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001011:Aorta / Q000502:physiology; D001161:Arteriosclerosis / Q000503:physiopathology* / Q000517:prevention & control / Q000662:veterinary; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000502:physiology; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology* / Q000662:veterinary; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D011817:Rabbits; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D014810:Vitamin E / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D000975:Antioxidants; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E