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

J Cell Mol Med. 2015 Jan;19(1):227-38. doi: 10.1111/jcmm.12442. Epub 2014 Nov 11.


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 (HUVECs) and angiogenesis in vitro and in vivo. Long-term treatment of HUVECs 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 H2 O2 -stressed cells. β-d-glucan-treated HUVECs 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. HUVECs overexpressing MnSOD demonstrated an increased activity of endothelial nitric oxide synthase (eNOS), reduced load of superoxide anion (O2 (-) ) 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 (HDACs 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 O2 (-) , 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.

Keywords: angiogenesis; antioxidants; beta-glucan; endothelial cells; histone deacetylases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Butyric Acid / pharmacology
  • Capillaries / drug effects
  • Capillaries / physiology
  • Cell Survival / drug effects
  • Cellular Microenvironment / drug effects*
  • Down-Regulation / drug effects
  • Histones / metabolism
  • Hordeum / chemistry*
  • Human Umbilical Vein Endothelial Cells / cytology*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / enzymology*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Neovascularization, Physiologic / drug effects*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Phosphorylation / drug effects
  • Superoxide Dismutase / metabolism*
  • Up-Regulation / drug effects
  • Zebrafish
  • beta-Glucans / pharmacology*


  • Histones
  • beta-Glucans
  • Butyric Acid
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase