Barley beta-glucan promotes MnSOD expression and enhances angiogenesis under oxidative microenvironment

Manganese superoxide dismutase (MnSOD), a foremost antioxidant enzyme, plays a key role in angiogenesis. Barley-derived (1.3) -d-glucan (-d-glucan) is a natural water-soluble polysaccharide with antioxidant properties. To explore the effects of -d-glucan on MnSOD-related angiogenesis under oxidative stress, we tested epigenetic mechanisms underlying modulation of MnSOD level in human umbilical vein endothelial cells (HUVECs) and angiogenesis in vitro and in vivo. Long-term treatment of HUVECs with 3% w/v -d-glucan significantly increased the level of MnSOD by 200%+/- 2% compared to control and by 50%+/- 4% compared to untreated H2O2-stressed cells. -d-glucan-treated HUVECs displayed greater angiogenic ability. In vivo, 24hrs-treatment with 3% w/v -d-glucan rescued vasculogenesis in Tg (kdrl: EGFP) s843Tg zebrafish embryos exposed to oxidative microenvironment. HUVECs overexpressing MnSOD demonstrated an increased activity of endothelial nitric oxide synthase (eNOS), reduced load of superoxide anion (O-2(-)) and an increased survival under oxidative stress. In addition, -d-glucan prevented the rise of hypoxia inducible factor (HIF)1- under oxidative stress. The level of histone H4 acetylation was significantly increased by -d-glucan. Increasing histone acetylation by sodium butyrate, an inhibitor of class I histone deacetylases (HDACs I), did not activate MnSOD-related angiogenesis and did not impair -d-glucan effects. In conclusion, 3% w/v -d-glucan activates endothelial expressionof MnSOD independent of histone acetylation level, thereby leading to adequate removal of O-2(-), cell survival and angiogenic response tooxidative stress. The identification of dietary -d-glucan as activator of MnSOD-related angiogenesis might lead to the development of nutritional approaches for the prevention of ischemic remodelling and heart failure.