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.