ARS | Publication request: Vitamin E Increases Production of Vasodilator Prostanoids in Human Aortic Endothelial Cells Through Opposing Effects on Cyclooxygenase-2 and Phospholipase A2

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 27, 2005
Publication Date: August 1, 2005
Citation: Wu, D., Liu, L., Maydani, M., Meydani, S.N. 2005. Vitamin E increases production of vasodilator prostanoids in human aortic endothelial cells through opposing effects on cyclooxygenase-2 and phospholipase A2. Journal of Nutrition. 135(8):1847-1853.

Interpretive Summary: Epidemiologic studies have suggested that increased vitamin E intake is associated with reduced morbidity and mortality from cardiovascular disease (CVD). Impairment of vasodilation or dilation of the blood vessels is associated with the initiation and development of atherosclerosis. The mechanism for this effect of vitamin E has been the subject of continuing investigation. Vitamin E has been shown to inhibit the various processes that contribute to atherosclerosis, a hallmark of CVD. One of key mechanisms underlying the action of vitamin E appears to be its ability to maintain or restore the endothelial cell function. In the current study, we determined the effect of in vitro vitamin E supplementation at physiologically relevant concentrations on the production of vasodilator prostanoids prostaglandin (PG)I2 and PGE2 by human aortic endothelial cells (HAEC) as well as its underlying mechanism. Results showed that vitamin E dose-dependently increased production of both prostanoids by HAEC. The vitamin E-induced increase in PGI2 and PGE2 production may contribute to its suggested beneficial effect in preserving endothelial function. This may be crucial scientific information since impairment of endothelium-dependent vasodilation is an early sign of atherosclerosis and its assessment has been proposed to have a prognostic value for CVD outcome in clinical practice.

Technical Abstract: 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 to 60 micromol/L) on production of vasodilator prostanoids prostaglandin (PG)I2 and PGE2 by human aortic endothelial cells (HAEC) as well as its underlying mechanism. Results showed that vitamin E dose-dependently (10 to 40 micromol/L) increased production of both prostanoids by HAEC. This was associated with a dose-dependent (10 to 40 micromol/L) up-regulation of cytosolic phospholipase A2 (cPLA2) expression and arachidonic acid release. In contrast, vitamin E dose-dependently (10 to 60 micromol/L) inhibited cyclooxygenase (COX) activity but did not affect 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 an opposite effect on the two key enzymes in prostanoid biosynthesis, which at the concentrations used in this study, resulted in a net increase in 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.