Vitamin E increases production of vasodilator prostanoids in human aortic endothelial cells through opposing effects on cyclooxygenase-2 and phospholipase A2.

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 micromol/L) on the production of the vasodilator prostanoids prostaglandin I(2) (PGI(2); prostacyclin) and prostaglandin E(2)(PGE(2)) by human aortic endothelial cells (HAECs) as well as its underlying mechanism. Results showed that vitamin E dose dependently (10-40 micromol/L) increased the production of both prostanoids by HAECs. This was associated with a dose-dependent (10-40 micromol/L) upregulation of cytosolic phospholipase A(2) (cPLA(2)) expression and arachidonic acid release. In contrast, vitamin E dose dependently (10-60 micromol/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 PGI(2) and PGE(2) production may contribute to its suggested beneficial effect in preserving endothelial function.