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) β‐ d ‐glucan (β‐ d ‐glucan) is a natural water‐soluble polysaccharide with antioxidant properties. To explore the effects of β‐ d ‐glucan on MnSOD ‐related angiogenesis under oxidative stress, we tested epigenetic mechanisms underlying modulation of MnSOD level in human umbilical vein endothelial cells ( HUVEC s) and angiogenesis in vitro and in vivo . Long‐term treatment of HUVEC s with 3% w/v β‐ d ‐glucan significantly increased the level of MnSOD by 200% ± 2% compared to control and by 50% ± 4% compared to untreated H 2 O 2 ‐stressed cells. β‐ d ‐glucan‐treated HUVEC s displayed greater angiogenic ability. In vivo , 24 hrs‐treatment with 3% w/v β‐ d ‐glucan rescued vasculogenesis in Tg ( kdrl: EGFP ) s843Tg zebrafish embryos exposed to oxidative microenvironment. HUVEC s 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, β‐ d ‐glucan prevented the rise of hypoxia inducible factor ( HIF )1‐α under oxidative stress. The level of histone H4 acetylation was significantly increased by β‐ d ‐glucan. Increasing histone acetylation by sodium butyrate, an inhibitor of class I histone deacetylases ( HDAC s I), did not activate MnSOD ‐related angiogenesis and did not impair β‐ d ‐glucan effects. In conclusion, 3% w/v β‐ d ‐glucan activates endothelial expression of MnSOD independent of histone acetylation level, thereby leading to adequate removal of O 2 − , cell survival and angiogenic response to oxidative stress. The identification of dietary β‐ 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.