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

  1. Julie Favre
  2. Emilie Vessieres
  3. Anne-Laure Guihot
  4. Coralyne Proux
  5. Linda Grimaud
  6. Jordan Rivron
  7. Manuela CL Garcia
  8. Léa Réthoré
  9. Rana Zahreddine
  10. Morgane Davezac
  11. Chanaelle Fébrissy
  12. Marine Adlanmerini
  13. Laurent Loufrani
  14. Vincent Procaccio
  15. Jean-Marie Foidart
  16. Gilles M Flouriot
  17. Francoise Lenfant
  18. Coralie Fontaine
  19. Jean-Françoise Arnal
  20. Daniel Henrion  Is a corresponding author
  1. Université d'Angers, France
  2. INSERM U1048, Paul Sabatier University (Toulouse III), France
  3. Université de Liège, Belgium
  4. INSERM U1085, IRSET (Institut de Recherche en Santé, Environnement et Travail), France

Abstract

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files are provided for each figure and supplement

Article and author information

Author details

  1. Julie Favre

    MITOVASC, CNRS UMR 6015, INSERM U1083, Université d'Angers, Angers, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Emilie Vessieres

    MITOVASC, CNRS UMR 6015, INSERM U1083, Université d'Angers, Angers, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Anne-Laure Guihot

    MITOVASC, CNRS UMR 6015, INSERM U1083, Université d'Angers, Angers, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Coralyne Proux

    MITOVASC, CNRS UMR 6015, INSERM U1083, Université d'Angers, Angers, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Linda Grimaud

    MITOVASC, CNRS UMR 6015, INSERM U1083, Université d'Angers, Angers, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Jordan Rivron

    MITOVASC, CNRS UMR 6015, INSERM U1083, Université d'Angers, Angers, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Manuela CL Garcia

    MITOVASC, CNRS UMR 6015, INSERM U1083, Université d'Angers, Angers, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Léa Réthoré

    MITOVASC, CNRS UMR 6015, INSERM U1083, Université d'Angers, Angers, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Rana Zahreddine

    Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), INSERM U1048, Paul Sabatier University (Toulouse III), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Morgane Davezac

    Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), INSERM U1048, Paul Sabatier University (Toulouse III), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Chanaelle Fébrissy

    Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), INSERM U1048, Paul Sabatier University (Toulouse III), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Marine Adlanmerini

    Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), INSERM U1048, Paul Sabatier University (Toulouse III), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Laurent Loufrani

    MITOVASC, CNRS UMR 6015, INSERM U1083, Université d'Angers, Angers, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3397-2335
  14. Vincent Procaccio

    MITOVASC, CNRS UMR 6015, INSERM U1083, Université d'Angers, Angers, France
    Competing interests
    The authors declare that no competing interests exist.
  15. Jean-Marie Foidart

    Groupe Interdisciplinaire de Génoprotéomique Appliquée, Université de Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  16. Gilles M Flouriot

    INSERM U1085, IRSET (Institut de Recherche en Santé, Environnement et Travail), Rennes, France
    Competing interests
    The authors declare that no competing interests exist.
  17. Francoise Lenfant

    Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), INSERM U1048, Paul Sabatier University (Toulouse III), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  18. Coralie Fontaine

    Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), INSERM U1048, Paul Sabatier University (Toulouse III), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  19. Jean-Françoise Arnal

    Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), INSERM U1048, Paul Sabatier University (Toulouse III), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  20. Daniel Henrion

    MITOVASC, CNRS UMR 6015, INSERM U1083, Université d'Angers, Angers, France
    For correspondence
    daniel.henrion@univ-angers.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1094-0285

Funding

Fondation pour la Recherche Médicale (FRM - DPC20171138957)

  • Daniel Henrion

Fondation pour la Recherche Médicale (Equipe FRM DEQ20160334924)

  • Jean-Françoise Arnal

Agence Nationale de la Recherche (ANR-18-CE14-0016-01)

  • Daniel Henrion

Fondation Lefoulon Delalande (N/A)

  • Julie Favre

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The investigation was conducted in accordance with the guidelines from Directive 2010/63/EU of the European Parliament for the protection of animals used for scientific purposes (authoriza-tion of the laboratory: # 00577). The protocol was approved by the Institutional Animal Care and Use Committee (IACUC): Committee on the Ethics of Animal Experiments (CEAA) of "Pays de la Loire" (permits #14335, #16740, and #16108).The mice were anesthetized with isoflurane (2.5%) and euthanized using a CO2 chamber and every effort was made to minimize suffering.

Reviewing Editor

  1. Noriaki Emoto, Kobe Pharmaceutical University, Japan

Publication history

  1. Received: March 23, 2021
  2. Accepted: November 26, 2021
  3. Accepted Manuscript published: November 29, 2021 (version 1)
  4. Version of Record published: December 16, 2021 (version 2)

Copyright

© 2021, Favre et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Julie Favre
  2. Emilie Vessieres
  3. Anne-Laure Guihot
  4. Coralyne Proux
  5. Linda Grimaud
  6. Jordan Rivron
  7. Manuela CL Garcia
  8. Léa Réthoré
  9. Rana Zahreddine
  10. Morgane Davezac
  11. Chanaelle Fébrissy
  12. Marine Adlanmerini
  13. Laurent Loufrani
  14. Vincent Procaccio
  15. Jean-Marie Foidart
  16. Gilles M Flouriot
  17. Francoise Lenfant
  18. Coralie Fontaine
  19. Jean-Françoise Arnal
  20. Daniel Henrion
(2021)
Membrane estrogen receptor alpha (ERα) participates in flow-mediated dilation in a ligand-independent manner
eLife 10:e68695.
https://doi.org/10.7554/eLife.68695

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