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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 (1060 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 (1040 µmol/L) increased the production of both prostanoids by HAECs. This was associated with a dose-dependent (1040 µmol/L) upregulation of cytosolic phospholipase A2 (cPLA2) expression and arachidonic acid release. In contrast, vitamin E dose dependently (1060 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 Einduced 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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