The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis.

Nuclear Factor-Kappa B [NFκB] activation triggers the elevation of various pro-angiogenic factors that contribute to the development and progression of diabetic vasculopathies. It has been demonstrated that vascular endothelial growth factor [VEGF] activates NFκB signaling pathway. Under the ischemi...

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Autores principales:	Michael DeNiro, Falah H Al-Mohanna, Osama Alsmadi, Futwan A Al-Mohanna
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/51432994845043539c9c6a992d49fb9c
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spelling	oai:doaj.org-article:51432994845043539c9c6a992d49fb9c2021-11-18T07:52:20ZThe nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis.1932-620310.1371/journal.pone.0059021https://doaj.org/article/51432994845043539c9c6a992d49fb9c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23533599/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Nuclear Factor-Kappa B [NFκB] activation triggers the elevation of various pro-angiogenic factors that contribute to the development and progression of diabetic vasculopathies. It has been demonstrated that vascular endothelial growth factor [VEGF] activates NFκB signaling pathway. Under the ischemic microenvironments, hypoxia-inducible factor-1 [HIF-1] upregulates the expression of several proangiogenic mediators, which play crucial roles in ocular pathologies. Whereas YC-1, a soluble guanylyl cyclase [sGC] agonist, inhibits HIF-1 and NFκB signaling pathways in various cell and animal models. Throughout this investigation, we examined the molecular link between VEGF and NFκB under a hypoxia-independent microenvironment in human retinal microvascular endothelial cells [hRMVECs]. Our data indicate that VEGF promoted retinal neovasculogenesis via NFκB activation, enhancement of its DNA-binding activity, and upregulating NFκB/p65, SDF-1, CXCR4, FAK, αVβ3, α5β1, EPO, ET-1, and MMP-9 expression. Conversely, YC-1 impaired the activation of NFκB and its downstream signaling pathways, via attenuating IκB kinase phosphorylation, degradation and activation, and thus suppressing p65 phosphorylation, nuclear translocation, and inhibiting NFκB-DNA binding activity. We report for the first time that the nexus between VEGF and NFκB is implicated in coordinating a scheme that upregulates several pro-angiogenic molecules, which promotes retinal neovasculogenesis. Our data may suggest the potential use of YC-1 to attenuate the deleterious effects that are associated with hypoxia/ischemia-independent retinal vasculopathies.Michael DeNiroFalah H Al-MohannaOsama AlsmadiFutwan A Al-MohannaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59021 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael DeNiro Falah H Al-Mohanna Osama Alsmadi Futwan A Al-Mohanna The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis.
description	Nuclear Factor-Kappa B [NFκB] activation triggers the elevation of various pro-angiogenic factors that contribute to the development and progression of diabetic vasculopathies. It has been demonstrated that vascular endothelial growth factor [VEGF] activates NFκB signaling pathway. Under the ischemic microenvironments, hypoxia-inducible factor-1 [HIF-1] upregulates the expression of several proangiogenic mediators, which play crucial roles in ocular pathologies. Whereas YC-1, a soluble guanylyl cyclase [sGC] agonist, inhibits HIF-1 and NFκB signaling pathways in various cell and animal models. Throughout this investigation, we examined the molecular link between VEGF and NFκB under a hypoxia-independent microenvironment in human retinal microvascular endothelial cells [hRMVECs]. Our data indicate that VEGF promoted retinal neovasculogenesis via NFκB activation, enhancement of its DNA-binding activity, and upregulating NFκB/p65, SDF-1, CXCR4, FAK, αVβ3, α5β1, EPO, ET-1, and MMP-9 expression. Conversely, YC-1 impaired the activation of NFκB and its downstream signaling pathways, via attenuating IκB kinase phosphorylation, degradation and activation, and thus suppressing p65 phosphorylation, nuclear translocation, and inhibiting NFκB-DNA binding activity. We report for the first time that the nexus between VEGF and NFκB is implicated in coordinating a scheme that upregulates several pro-angiogenic molecules, which promotes retinal neovasculogenesis. Our data may suggest the potential use of YC-1 to attenuate the deleterious effects that are associated with hypoxia/ischemia-independent retinal vasculopathies.
format	article
author	Michael DeNiro Falah H Al-Mohanna Osama Alsmadi Futwan A Al-Mohanna
author_facet	Michael DeNiro Falah H Al-Mohanna Osama Alsmadi Futwan A Al-Mohanna
author_sort	Michael DeNiro
title	The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis.
title_short	The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis.
title_full	The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis.
title_fullStr	The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis.
title_full_unstemmed	The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis.
title_sort	nexus between vegf and nfκb orchestrates a hypoxia-independent neovasculogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/51432994845043539c9c6a992d49fb9c
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The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis.

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