α-Tocopherol, especially α-tocopherol phosphate, exerts antiapoptotic and angiogenic effects on rat bone marrow-derived endothelial progenitor cells under high-glucose and hypoxia conditions

Abstract

α-T, especially α-TP, possesses therapeutic potential in the inhibition of apoptosis and increases the migratory capacity of EPCs under high-glucose/hypoxic conditions. It promotes angiogenesis by upregulating Bcl-2, Akt, and vascular endothelial growth factor receptor 2 and decreasing nuclear factor κB p65, p38MAPK, Notch-1, JNK, and Tie-2.

Vitamin E: Regulatory role in the cardiovascular system

“…In this system, α-TP was shown to reduce the proliferation of THP-1 monocytes while α-tocopherol had no significant effect (102). Wu et al (103) showed α-TP, more effectively than α-tocopherol, inhibits apoptosis and enhances migration and capillary tube structure formation in endothelial progenitor cells under high glucose/hypoxic conditions. In another study, α-TP enhanced the promoter activity of human vascular endothelial growth factor, more effectively than α-tocopherol (104) which suggests α-TP might be involved in vasculogenesis and angiogenesis (105).…”

OGR1 mediates the inhibitory effects of acidic environment on proliferation and angiogenesis of endothelial progenitor cells

“…Kim et al (2018) found that a hypoxic microenvironment can promote proliferation, migration, and angiogenesis of human EPCs through mitochondrial division and related signaling pathways. However, Wu et al (2018) found that proliferation, migration, and angiogenesis of rat bone marrow-derived EPCs were inhibited in a high glucose micro-environment with hypoxia. In this study, proliferation, migration, and vascularization of EPCs were inhibited in a pH 6.4 environment as determined by transwell, scratch test, and tube-forming experiments.…”

Vitamin E: Regulatory Role on Signal Transduction

“…Low concentrations of αTP increase generation of regulatory ROS possibly as result of αTP‐mediated conversion of cytochrome c into a peroxidating enzyme producing H 2 O 2 . In fact, αTP decreased apoptosis, enhanced cell migration and capillary tube formation in human brain microvascular endotheliocytes (HBME) and in rat bone marrow‐derived endothelial progenitor cells under high‐glucose and hypoxia conditions by up‐regulating the expression of Bcl‐2, Akt and the VEGF receptor and by decreasing NFκB p65, p38MAPK, Notch‐1, JNK, and Tie‐2 . Likewise, in a rat ischemia/reperfusion injury model, αTP prevented apoptosis by normalizing reduced phosphorylation of Akt, p38 MAPKβ, p44/42 mitogen activated kinase β (MAPK), and NFκB binding, and decreased phosphorylation of Src and MAPKα .…”

“…Thus, the stimulatory effect of αT on angiogenesis and vasculogenesis can be potentiated by phosphorylation to αTP, which may act as an active lipid mediator increasing VEGF expression. In addition to its essential effects against fetal resorption and reproduction, the induction of VEGF and VEGF receptor by vitamin E may contribute to the prevention of ischemia/reperfusion injury in the cardiovascular and nervous system and stimulate cellular migration, tissue repair and regeneration , enhance reparative angiogenesis and tissue remodeling after experimental myocardial infarction , promote survival of muscle cells and neurons, stimulate neurite outgrowth, and prevent neurodegenerative processes . These regulatory effects on VEGF expression may contribute to the preventive effects of vitamin E in a number of diseases in which VEGF levels are reduced including atherosclerosis, diabetes, pre‐eclampsia, neurodegenerative disease, and wound healing .…”