Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice

Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) is a regulator of mitochondrial oxidative metabolism and reactive oxygen species (ROS) homeostasis that is known to be inactivated in diabetic subjects. This study aimed to investigate the contribution of PGC-1α inactivation to th...

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Authors: García-Quintans, Nieves, Sánchez-Ramos, Cristina, Prieto, Ignacio, Tierrez, Albert, Arza, Elvira, Alfranca, Arántzazu, Redondo, Juan Miguel, Monsalve, María
Format: article
Status:Versión enviada para evaluación y publicación
Publication Date:2016
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/150943
Online Access:http://hdl.handle.net/10261/150943
Access Level:Open access
Keyword:Vascular stability
ROS
Angiogenesis
Retinopathy
PGC-1α
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spelling Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient miceGarcía-Quintans, NievesSánchez-Ramos, CristinaPrieto, IgnacioTierrez, AlbertArza, ElviraAlfranca, ArántzazuRedondo, Juan MiguelMonsalve, MaríaVascular stabilityROSAngiogenesisRetinopathyPGC-1αPeroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) is a regulator of mitochondrial oxidative metabolism and reactive oxygen species (ROS) homeostasis that is known to be inactivated in diabetic subjects. This study aimed to investigate the contribution of PGC-1α inactivation to the development of oxygen-induced retinopathy. We analyzed retinal vascular development in PGC-1α mice. Retinal vasculature of PGC-1α mice showed reduced pericyte coverage, a de-structured vascular plexus, and low perfusion. Exposure of PGC-1α mice to hyperoxia during retinal vascular development exacerbated these vascular abnormalities, with extensive retinal hemorrhaging and highly unstructured areas as compared with wild-type mice. Structural analysis demonstrated a reduction in membrane-bound VE-cadherin, which was suggestive of defective intercellular junctions. Interestingly, PGC-1α retinas showed a constitutive activation of the VEGF-A signaling pathway. This phenotype could be partially reversed by antioxidant administration, indicating that elevated production of ROS in the absence of PGC-1α could be a relevant factor in the alteration of the VEGF-A signaling pathway. Collectively, our findings suggest that PGC-1α control of ROS homeostasis plays an important role in the regulation of de novo angiogenesis and is required for vascular stability.This work was supported by grants from the Spanish ‘‘Ministerio de Economía y Competitividad’’ (Grant number SAF2009-07599 & SAF2012-37693 to M.M and CSD 2007-00020 to M.M.) and the ‘‘Comunidad de Madrid’’ (Grant Number S2010/BMD-2361 to M.M.).Peer ReviewedSpringer NatureComunidad de MadridMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720162017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Preprintinfo:eu-repo/semantics/submittedVersionhttp://hdl.handle.net/10261/150943reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#S2010/BMD-2361/PRIMPOLhttps://doi.org/10.1007/s10456-016-9502-0Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1509432026-05-22T06:33:51Z
dc.title.none.fl_str_mv Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice
title Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice
spellingShingle Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice
García-Quintans, Nieves
Vascular stability
ROS
Angiogenesis
Retinopathy
PGC-1α
title_short Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice
title_full Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice
title_fullStr Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice
title_full_unstemmed Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice
title_sort Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice
dc.creator.none.fl_str_mv García-Quintans, Nieves
Sánchez-Ramos, Cristina
Prieto, Ignacio
Tierrez, Albert
Arza, Elvira
Alfranca, Arántzazu
Redondo, Juan Miguel
Monsalve, María
author García-Quintans, Nieves
author_facet García-Quintans, Nieves
Sánchez-Ramos, Cristina
Prieto, Ignacio
Tierrez, Albert
Arza, Elvira
Alfranca, Arántzazu
Redondo, Juan Miguel
Monsalve, María
author_role author
author2 Sánchez-Ramos, Cristina
Prieto, Ignacio
Tierrez, Albert
Arza, Elvira
Alfranca, Arántzazu
Redondo, Juan Miguel
Monsalve, María
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Comunidad de Madrid
Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Vascular stability
ROS
Angiogenesis
Retinopathy
PGC-1α
topic Vascular stability
ROS
Angiogenesis
Retinopathy
PGC-1α
description Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) is a regulator of mitochondrial oxidative metabolism and reactive oxygen species (ROS) homeostasis that is known to be inactivated in diabetic subjects. This study aimed to investigate the contribution of PGC-1α inactivation to the development of oxygen-induced retinopathy. We analyzed retinal vascular development in PGC-1α mice. Retinal vasculature of PGC-1α mice showed reduced pericyte coverage, a de-structured vascular plexus, and low perfusion. Exposure of PGC-1α mice to hyperoxia during retinal vascular development exacerbated these vascular abnormalities, with extensive retinal hemorrhaging and highly unstructured areas as compared with wild-type mice. Structural analysis demonstrated a reduction in membrane-bound VE-cadherin, which was suggestive of defective intercellular junctions. Interestingly, PGC-1α retinas showed a constitutive activation of the VEGF-A signaling pathway. This phenotype could be partially reversed by antioxidant administration, indicating that elevated production of ROS in the absence of PGC-1α could be a relevant factor in the alteration of the VEGF-A signaling pathway. Collectively, our findings suggest that PGC-1α control of ROS homeostasis plays an important role in the regulation of de novo angiogenesis and is required for vascular stability.
publishDate 2016
dc.date.none.fl_str_mv 2016
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Preprint
info:eu-repo/semantics/submittedVersion
format article
status_str submittedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/150943
url http://hdl.handle.net/10261/150943
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
S2010/BMD-2361/PRIMPOL
https://doi.org/10.1007/s10456-016-9502-0
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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