Vitamins and regulation of angiogenesis: [A, B1, B2, B3, B6, B9, B12, C, D, E, K]

Abstract Angiogenesis is one of the most important processes during wound healing, tissue regeneration, and tumor growth. Vitamins are one of the most important micronutrients, which play great roles in many biochemical reactions inside the cells and cell pathways affecting various cellular functions. Here the effects of essential vitamins on angiogenesis are overviewed. An electronic search was performed in PubMed database via OVID from January 2000 to February 2017 using the keywords regarding the effects of vitamins on angiogenesis. Of the 911 articles found in our initial search only 126 met the inclusion criteria. Vitamin A, both 13-cis retinoid acid and acyclic acid inhibit angiogenesis by suppressing VEGF, while all trans retinoid acid induces angiogenesis by enhancing the expression of proangiogenic factors and reducing pro-MMP2 activity. Vitamin B1, Thiamine, simulates angiogenesis by inducing proliferation of human endothelial progenitor cells and inhibiting apoptosis via PKB/Akt-mediated potentiation. Vitamin B2, Riboflavin, inhibits angiogenesis by decreasing phosphorylation of Src tyrosine 16, an activator residue of Src kinase, and a key player in angiogenesis. Vitamin B3, Niacin, acts as a proangiogenic substance by acting as a precursor of NAD+, as well as promoting endothelial cell function via its receptor GPR109A. Vitamin B6 inhibits angiogenesis by inhibiting micro vessel outgrowth and suppressing the proliferation of endothelial cells. Vitamin B9, Folic acid, inhibits angiogenesis by decreasing proliferation of endothelial cells, as well as activating Src/ERK2/NF-κB/p53 signaling pathways, resulting in cell cycle arrest. Vitamin B12, Cobalamin, acts as a pro-angiogenic substance by inducing production of NO, prostaglandin E1, and prostacyclin leading to angiogenesis. Furthermore, vitamin B12 reduces homocysteine levels in plasma, which is a significant anti-angiogenesis agent. Vitamin C in high concentrations alters the metabolic activity of endothelial cells; decreasing their ATP levels and cell proliferation. Thus, vitamin C has anti-angiogenic properties. Vitamin D in the 1,25D3 form has anti-proliferative effects by inducing cell cycle arrest and apoptosis. Vitamin E, Tocopherols, exhibit anti-angiogenic effects by inhibition of proliferation and tube formation of endothelial cells through suppression of signaling pathways that are dependent on activation of PI3K/PDK/Akt signaling. Vitamin K exhibits its antiangiogenic activity by acting on protein S, through inhibition of vascular endothelial growth factor-receptor 2 (VEGFR2)-dependent vascularization as well as VEGF induced endothelial cell migration and proliferation. According to the studies evaluated here, vitamins A, B, C, D, E and K exhibit pro- or anti-angiogenic activities based on their derivatives and physiological settings. Vitamin A shows both anti- and pro-angiogenesis activity while Vitamins B2, B6, B9, C, D, E and K have anti-angiogenic properties and Vitamins B1 and B3 are proangiogenesis.