α‐Tocopheryl phosphate – an activated form of vitamin E important for angiogenesis?

Vitamin E (α‐tocopherol, αT) was originally discovered as a dietary factor essential for reproduction in rats. The molecular basis for reproductive failure during vitamin E deficiency was later described to be associated with impaired formation of an extensive placental vascular network. Recently, small amounts of a novel αT derivative, alpha‐tocopheryl phosphate (αTP), have been detected in plasma and animal tissues as well as in foods. We have now assessed the effects of αT and αTP on gene expression in THP‐1 monocytes using gene arrays. The expression of the vascular endothelial growth factor (VEGF) was induced by αTP at mRNA and protein level leading to enhanced angiogenesis in HUVEC cells. Induction of VEGF by αTP was the consequence of stimulation of the PI3K/Akt signalling pathway. The treatment with αTP, but not with αT, significantly induced a VEGF‐promoter luciferase construct transfected into HEK293 cells. We propose that αT is activated by phosphorylation to αTP which may act as an active cofactor or lipid mediator influencing cellular signaling and gene expression leading, in selected tissues, to increased angiogenesis and most likely vasculogenesis. Increased VEGF expression induced by αTP may explain not only the essential effects of vitamin E on reproduction, but also increased cell survival during ischemia/reperfusion injury in brain and muscle cells. Supported by USDA Contract #58‐1950‐7‐707 .