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Biochemical and Molecular Actions of Nutrients

Vitamin E Increases Production of Vasodilator Prostanoids in Human Aortic Endothelial Cells through Opposing Effects on Cyclooxygenase-2 and Phospholipase A₂^1,2

Nutritional Immunology Laboratory and ^* Vascular Biology Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111

³To whom correspondence should be addressed. E-mail: dayong.wu{at}tufts.edu.

Impairment of endothelium-dependent vasodilation is associated with the initiation and development of atherosclerosis. Vasodilator prostanoids constitute a protective mechanism in maintaining normal vasomotor function. In the current study, we determined the effect of in vitro vitamin E supplementation at physiologically relevant concentrations (10–60 µmol/L) on the production of the vasodilator prostanoids prostaglandin I₂ (PGI₂; prostacyclin) and prostaglandin E₂(PGE₂) by human aortic endothelial cells (HAECs) as well as its underlying mechanism. Results showed that vitamin E dose dependently (10–40 µmol/L) increased the production of both prostanoids by HAECs. This was associated with a dose-dependent (10–40 µmol/L) upregulation of cytosolic phospholipase A₂ (cPLA₂) expression and arachidonic acid release. In contrast, vitamin E dose dependently (10–60 µmol/L) inhibited cyclooxygenase (COX) activity but did not affect the expression of either COX-1 or COX-2, indicating that the effect of vitamin E on COX activity was post-translational. Thus, vitamin E had opposing effects on the 2 key enzymes in prostanoid biosynthesis; at the concentrations used in this study, this resulted in a net increase in the production of vasodilator prostanoids. The vitamin E–induced increase in PGI₂ and PGE₂ production may contribute to its suggested beneficial effect in preserving endothelial function.

KEY WORDS: • vitamin E • human aorta endothelial cells • prostanoids • cyclooxygenase • phospholipase A₂

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