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.
Wu
Dayong
D
Nutritional Immunology Laboratory, Jean Mayer U.S Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. dayong.wu@tufts.edu
Liu
Liping
L
Meydani
Mohsen
M
Meydani
Simin Nikbin
SN
D001011:Aorta; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D024502:alpha-Tocopherol / Q000494:pharmacology*
D008565:Membrane Proteins; D016718:Arachidonic Acid; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D024502:alpha-Tocopherol; D015232:Dinoprostone