Membrane estrogen receptor alpha (ERα) participates in flow-mediated dilation in a ligand-independent manner

Estrogen receptor alpha (ERα) activation by estrogens prevents atheroma through its nuclear action, whereas plasma membrane-located ERα accelerates endothelial healing. The genetic deficiency of ERα was associated with a reduction in flow-mediated dilation (FMD) in one man. Here, we evaluated ex viv...

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Main Authors: Julie Favre, Emilie Vessieres, Anne-Laure Guihot, Coralyne Proux, Linda Grimaud, Jordan Rivron, Manuela CL Garcia, Léa Réthoré, Rana Zahreddine, Morgane Davezac, Chanaelle Fébrissy, Marine Adlanmerini, Laurent Loufrani, Vincent Procaccio, Jean-Michel Foidart, Gilles Flouriot, Françoise Lenfant, Coralie Fontaine, Jean-François Arnal, Daniel Henrion
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/68695
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author Julie Favre
Emilie Vessieres
Anne-Laure Guihot
Coralyne Proux
Linda Grimaud
Jordan Rivron
Manuela CL Garcia
Léa Réthoré
Rana Zahreddine
Morgane Davezac
Chanaelle Fébrissy
Marine Adlanmerini
Laurent Loufrani
Vincent Procaccio
Jean-Michel Foidart
Gilles Flouriot
Françoise Lenfant
Coralie Fontaine
Jean-François Arnal
Daniel Henrion
author_facet Julie Favre
Emilie Vessieres
Anne-Laure Guihot
Coralyne Proux
Linda Grimaud
Jordan Rivron
Manuela CL Garcia
Léa Réthoré
Rana Zahreddine
Morgane Davezac
Chanaelle Fébrissy
Marine Adlanmerini
Laurent Loufrani
Vincent Procaccio
Jean-Michel Foidart
Gilles Flouriot
Françoise Lenfant
Coralie Fontaine
Jean-François Arnal
Daniel Henrion
author_sort Julie Favre
collection DOAJ
description Estrogen receptor alpha (ERα) activation by estrogens prevents atheroma through its nuclear action, whereas plasma membrane-located ERα accelerates endothelial healing. The genetic deficiency of ERα was associated with a reduction in flow-mediated dilation (FMD) in one man. Here, we evaluated ex vivo the role of ERα on FMD of resistance arteries. FMD, but not agonist (acetylcholine, insulin)-mediated dilation, was reduced in male and female mice lacking ERα (Esr1-/- mice) compared to wild-type mice and was not dependent on the presence of estrogens. In C451A-ERα mice lacking membrane ERα, not in mice lacking AF2-dependent nuclear ERα actions, FMD was reduced, and restored by antioxidant treatments. Compared to wild-type mice, isolated perfused kidneys of C451A-ERα mice revealed a decreased flow-mediated nitrate production and an increased H2O2 production. Thus, endothelial membrane ERα promotes NO bioavailability through inhibition of oxidative stress and thereby participates in FMD in a ligand-independent manner.
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spelling doaj.art-9a36969e61414a318a017f8e1eddcd912022-12-22T02:01:59ZengeLife Sciences Publications LtdeLife2050-084X2021-11-011010.7554/eLife.68695Membrane estrogen receptor alpha (ERα) participates in flow-mediated dilation in a ligand-independent mannerJulie Favre0Emilie Vessieres1Anne-Laure Guihot2Coralyne Proux3Linda Grimaud4Jordan Rivron5Manuela CL Garcia6Léa Réthoré7Rana Zahreddine8Morgane Davezac9Chanaelle Fébrissy10Marine Adlanmerini11Laurent Loufrani12https://orcid.org/0000-0003-3397-2335Vincent Procaccio13Jean-Michel Foidart14Gilles Flouriot15Françoise Lenfant16Coralie Fontaine17Jean-François Arnal18Daniel Henrion19https://orcid.org/0000-0003-1094-0285Angers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, FranceAngers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France; CARFI facility, Angers University, Angers, FranceAngers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France; CARFI facility, Angers University, Angers, FranceAngers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France; CARFI facility, Angers University, Angers, FranceAngers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, FranceAngers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France; CARFI facility, Angers University, Angers, FranceAngers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France; CARFI facility, Angers University, Angers, FranceAngers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, FranceINSERM U1297, Paul Sabatier University (Toulouse III) , University Hospital (UHC) of Toulouse, Toulouse, FranceINSERM U1297, Paul Sabatier University (Toulouse III) , University Hospital (UHC) of Toulouse, Toulouse, FranceINSERM U1297, Paul Sabatier University (Toulouse III) , University Hospital (UHC) of Toulouse, Toulouse, FranceINSERM U1297, Paul Sabatier University (Toulouse III) , University Hospital (UHC) of Toulouse, Toulouse, FranceAngers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France; University Hospital (CHU) of Angers, Angers, FranceAngers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France; University Hospital (CHU) of Angers, Angers, FranceGroupe Interdisciplinaire de Génoprotéomique Appliquée, Université de Liège, Liège, BelgiumINSERM U1085, IRSET (Institut de Recherche en Santé, Environnement et Travail), University of Rennes, Rennes, FranceINSERM U1297, Paul Sabatier University (Toulouse III) , University Hospital (UHC) of Toulouse, Toulouse, FranceINSERM U1297, Paul Sabatier University (Toulouse III) , University Hospital (UHC) of Toulouse, Toulouse, FranceINSERM U1297, Paul Sabatier University (Toulouse III) , University Hospital (UHC) of Toulouse, Toulouse, FranceAngers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France; CARFI facility, Angers University, Angers, France; University Hospital (CHU) of Angers, Angers, FranceEstrogen receptor alpha (ERα) activation by estrogens prevents atheroma through its nuclear action, whereas plasma membrane-located ERα accelerates endothelial healing. The genetic deficiency of ERα was associated with a reduction in flow-mediated dilation (FMD) in one man. Here, we evaluated ex vivo the role of ERα on FMD of resistance arteries. FMD, but not agonist (acetylcholine, insulin)-mediated dilation, was reduced in male and female mice lacking ERα (Esr1-/- mice) compared to wild-type mice and was not dependent on the presence of estrogens. In C451A-ERα mice lacking membrane ERα, not in mice lacking AF2-dependent nuclear ERα actions, FMD was reduced, and restored by antioxidant treatments. Compared to wild-type mice, isolated perfused kidneys of C451A-ERα mice revealed a decreased flow-mediated nitrate production and an increased H2O2 production. Thus, endothelial membrane ERα promotes NO bioavailability through inhibition of oxidative stress and thereby participates in FMD in a ligand-independent manner.https://elifesciences.org/articles/68695endotheliumshear stressestrogen receptorsblood flowresistance arteries
spellingShingle Julie Favre
Emilie Vessieres
Anne-Laure Guihot
Coralyne Proux
Linda Grimaud
Jordan Rivron
Manuela CL Garcia
Léa Réthoré
Rana Zahreddine
Morgane Davezac
Chanaelle Fébrissy
Marine Adlanmerini
Laurent Loufrani
Vincent Procaccio
Jean-Michel Foidart
Gilles Flouriot
Françoise Lenfant
Coralie Fontaine
Jean-François Arnal
Daniel Henrion
Membrane estrogen receptor alpha (ERα) participates in flow-mediated dilation in a ligand-independent manner
eLife
endothelium
shear stress
estrogen receptors
blood flow
resistance arteries
title Membrane estrogen receptor alpha (ERα) participates in flow-mediated dilation in a ligand-independent manner
title_full Membrane estrogen receptor alpha (ERα) participates in flow-mediated dilation in a ligand-independent manner
title_fullStr Membrane estrogen receptor alpha (ERα) participates in flow-mediated dilation in a ligand-independent manner
title_full_unstemmed Membrane estrogen receptor alpha (ERα) participates in flow-mediated dilation in a ligand-independent manner
title_short Membrane estrogen receptor alpha (ERα) participates in flow-mediated dilation in a ligand-independent manner
title_sort membrane estrogen receptor alpha erα participates in flow mediated dilation in a ligand independent manner
topic endothelium
shear stress
estrogen receptors
blood flow
resistance arteries
url https://elifesciences.org/articles/68695
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