Background: Angiogenic response of adult endothelial cells can significantly improve the repair potential of ischemic myocardium; however, it is challenging topromote it in the presence of oxidative stress. We recently demonstrated that increased global histone H4 acetylation promotes angiogenesis under oxidative microenvironment; thus, the identification of novel natural angiomodulators is a desirable achievement. Barley-derived (1.3)beta-D-glucan (β-D-glucan) is a watersoluble chain of D-glucose polysaccharide with antioxidant properties, but its angiogenic effect is still unknown. We investigated whether the conditioning of adult endothelial cells with β-D-glucan enhances the angiogenic response to oxidative stress involving histone H4 acetylation. Methods: In vitro, human umbilical vein endothelial cells (HUVECs) chronically exposed to H2O2 (50uM for 24h) were cultured with or without 3% w/v β-D-glucan, then tested for cell viability and tube formation. p-eNOS/eNOS ratio, pAkt/Akt ratio, HIF1-alpha and MnSOD expression, and the level of histone H4 acetylation were evaluated. In vivo, Tg(kdrl:EGFP)s843Tg transgenic zebrafish embryos were treated for 24h with 3% w/v β-D-glucan under oxidative microenvironment prior angiogenesis assay. Results: HUVECs treatment with β-D-glucan prevented cell death by 87.41±14% (P≤0.004) and significantly increased tube formation activity by 11±4% under oxidative microenvironment. At the cellular level such effects seem to be mediated by an epigenetic induction of MnSOD expression through significant increase of histone H4 acetylation (+410±34.3%). Finally, similar dose of β-D-glucan was confirmed to prevent vascular depletion in zebrafish embryos chronically exposed to oxidative microenvironment. Conclusions: Our study revealed, for the first time, that barley-derived β-Dglucan promotes adult angiogenesis under oxidative microenvironment through increased histone H4 acetylation. These findings uncover a novel and unexpected role for dietary β-D-glucan as a critical epigenetic activator of antioxidant activity governing adult angiogenic response.
Barley-derived (1.3) beta-D-glucans promotes angiogenesis involving histone H4 acetylation in human endothelial cells and zebrafish under oxidative microenvironment
AGOSTINI, Silvia;LIONETTI, Vincenzo
2014-01-01
Abstract
Background: Angiogenic response of adult endothelial cells can significantly improve the repair potential of ischemic myocardium; however, it is challenging topromote it in the presence of oxidative stress. We recently demonstrated that increased global histone H4 acetylation promotes angiogenesis under oxidative microenvironment; thus, the identification of novel natural angiomodulators is a desirable achievement. Barley-derived (1.3)beta-D-glucan (β-D-glucan) is a watersoluble chain of D-glucose polysaccharide with antioxidant properties, but its angiogenic effect is still unknown. We investigated whether the conditioning of adult endothelial cells with β-D-glucan enhances the angiogenic response to oxidative stress involving histone H4 acetylation. Methods: In vitro, human umbilical vein endothelial cells (HUVECs) chronically exposed to H2O2 (50uM for 24h) were cultured with or without 3% w/v β-D-glucan, then tested for cell viability and tube formation. p-eNOS/eNOS ratio, pAkt/Akt ratio, HIF1-alpha and MnSOD expression, and the level of histone H4 acetylation were evaluated. In vivo, Tg(kdrl:EGFP)s843Tg transgenic zebrafish embryos were treated for 24h with 3% w/v β-D-glucan under oxidative microenvironment prior angiogenesis assay. Results: HUVECs treatment with β-D-glucan prevented cell death by 87.41±14% (P≤0.004) and significantly increased tube formation activity by 11±4% under oxidative microenvironment. At the cellular level such effects seem to be mediated by an epigenetic induction of MnSOD expression through significant increase of histone H4 acetylation (+410±34.3%). Finally, similar dose of β-D-glucan was confirmed to prevent vascular depletion in zebrafish embryos chronically exposed to oxidative microenvironment. Conclusions: Our study revealed, for the first time, that barley-derived β-Dglucan promotes adult angiogenesis under oxidative microenvironment through increased histone H4 acetylation. These findings uncover a novel and unexpected role for dietary β-D-glucan as a critical epigenetic activator of antioxidant activity governing adult angiogenic response.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
