Antioxidant vitamins induce angiogenesis in the normal pig kidney

Abstract

The effects of chronic supplementation with antioxidant vitamins on angiogenesis are controversial. The aim of the present study was to evaluate in kidneys of normal pigs the effect of chronic supplementation with vitamins E and C, at doses that are effective in reducing oxidative stress and attenuating angiogenesis under pathological conditions. Domestic pigs were randomized to receive a 12-wk normal diet without ( n = 6) or with antioxidant vitamins supplementation (1g/day vitamin C, 100 IU·kg−1·day−1 vitamin E; n = 6). Electron beam computed tomography (CT) was used to evaluate renal cortical vascular function in vivo, and micro-CT was to assess the spatial density and average diameter of cortical microvessels (diameter <500 μm) ex vivo. Oxidative stress and expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α were evaluated in renal tissue. The effects of increasing concentrations of the same vitamins on redox status and angiogenesis were also evaluated in human umbilical vascular endothelial cells (HUVEC). Compared with normal pigs, the density of cortical transmural microvessels was significantly greater in vitamin-supplemented pigs (149.0 ± 11.7 vs. 333.8 ± 48.1 vessel/cm2, P < 0.05), whereas the cortical perfusion response to ACh was impaired. This was accompanied by a significant increase in tissue oxidative stress and levels of VEGF and HIF-1α. A low dose of antioxidant decreased, whereas a high dose increased, HUVEC oxidative stress and angiogenesis, which was partly mediated by hydrogen peroxide. Antioxidant vitamin supplementation can increase tissue oxidative redox and microvascular proliferation in the normal kidney, probably due to a biphasic effect that depends on basal redox balance.

α‐Tocopheryl phosphate—An activated form of vitamin E important for angiogenesis and vasculogenesis?

“…In monocytes/macrophages, the observed stimulation of VEGF production may enhance reparative angiogenesis and tissue remodeling as observed after experimental myocardial infarction occurring in a PI3Kc/Aktdependent manner [74]. Similar to that, increased VEGF expression and angiogenesis observed in the kidneys of normal pigs supplemented with vitamins E and C may be the result of the formation of aTP [59,60]. In the placenta, the stimulation of VEGF expression and vasculogenesis by aTP may explain the essentiality of vitamin E against fetal resorption.…”

“…Interestingly, vitamin E has been reported to induce expression of HIF-1a, leading to induction of VEGF via the hypoxia response element on the VEGF promoter; however, whether this effect occurs as a consequence of aTP formation [59,60] was not evaluated. In the placenta, hypoxia appears to occur only at the beginning of embryonic development [107,108].…”

“…Regulation of VEGF expression by vitamin E has been reported in several in vitro and in vivo experimental systems, in which either activation [59,60] or inhibition of VEGF [61,62] has been observed, but the molecular mechanisms of VEGF modulation are not clear. In human microvascular endothelial cells, angiogenesis was inhibited by aT through suppressing the expression of interleukin 8 (IL-8), which is an angiogenic cytokine [63].…”

Coenzyme Q10 Decreases TNF-α and IL-2 Secretion by Human Peripheral Blood Mononuclear Cells

“…However, a higher dose (10 M) of CoQ10 did not affect the secretion of either TNF-␣ or IL-2. It is possible that this phenomenon may be explained by the anti-oxidant effect of CoQ10, as has been reported by Daghini et al (25), who have shown (26,27). Thus, Sohal et al (28) have shown that, although supplementation of CoQ10 to mice increased its endogenous content, the rate of superoxide anion generation determined in various tissues did not differ significantly from that in controls.…”

Hypoxia-Inducible Factor-1.ALPHA. Is Involved in the Pro-angiogenic Effect of Hydrogen Sulfide under Hypoxic Stress

“…17) VSMCs were plated on the underside of a Transwell insert. Once VSMCs reached confluence, the Transwell insert was inverted, and ECs were plated onto the top side for 2 d. Four sets of experiments were performed: (1) non-VSMCs, endothelial cells without co-culture with VSMC, (2) Vehicle, untreated cocultured cells, (3) CoCl 2 , cells treated with CoCl 2 (300 mM), and (4) H 2 S, co-culture cells pre-treated with H 2 S (300 mM) for 1 h before incubating with CoCl 2 (300 mM).…”