SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization.

Abstract

SIRT1, a NAD(+) -dependent histone deacetylase, has been shown to act as a key regulator of angiogenesis. The purpose of this study was to determine the effects of resveratrol (RSV, a SIRT1 activator) on the vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway and to establish its relevance to choroidal neovascularization (CNV), a blinding complication of age-related macular degeneration. Western blot and ELISA assay showed that RSV inhibited hypoxia-inducible factor (HIF)-1α accumulation and VEGF secretion induced by cobalt chloride (CoCl2) through SIRT1 in human retinal pigment epithelial (hRPE) cells. Furthermore, RSV down-regulated VEGFR2 phosphorylation and activation induced by VEGF in endothelial cells via SIRT1. Thus, the inhibitory effect of RSV on the HIF-1α/VEGF/VEGFR2 signaling axis is mediated, at least in part, through SIRT1. The results suggest that targeting SIRT1 could have therapeutic potential for the treatment of CNV.

• Authors: Huiming Zhang, Shikun He, Christine Spee, Keijiro Ishikawa, David R Hinton
• Journal: Cytokine (Cytokine) Vol. 76 Issue 2 Pg. 549-552 (Dec 2015) ISSN: 1096-0023 [Electronic] England
• PMID: 26174951 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Stilbenes
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factor Receptor-2
• SIRT1 protein, human
• Sirtuin 1
• Resveratrol

Topics

• Cell Line
• Choroidal Neovascularization (physiopathology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors)
• Phosphorylation
• Resveratrol
• Signal Transduction (drug effects)
• Sirtuin 1 (physiology)
• Stilbenes (pharmacology)
• Vascular Endothelial Growth Factor A (metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (metabolism)