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

eLife

Léa Réthoré¹  Linda Grimaud¹  Julie Favre¹  Anne-Laure Guihot²  Manuela CL Garcia²  Emilie Vessieres²  Jordan Rivron²  Coralyne Proux²  Daniel Henrion³  Vincent Procaccio⁴  Laurent Loufrani⁴  Jean-Michel Foidart⁵  Gilles Flouriot⁶  Morgane Davezac⁷  Jean-François Arnal⁷  Marine Adlanmerini⁷  Coralie Fontaine⁷  Rana Zahreddine⁷  Chanaelle Fébrissy⁷  Françoise Lenfant⁷ 

[1] Angers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France;Angers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France;CARFI facility, Angers University, Angers, France;Angers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France;CARFI facility, Angers University, Angers, France;University Hospital (CHU) of Angers, Angers, France;Angers University, MITOVASC, CNRS UMR 6015, INSERM U1083, Angers, France;University Hospital (CHU) of Angers, Angers, France;Groupe Interdisciplinaire de Génoprotéomique Appliquée, Université de Liège, Liège, Belgium;INSERM U1085, IRSET (Institut de Recherche en Santé, Environnement et Travail), University of Rennes, Rennes, France;INSERM U1297, Paul Sabatier University (Toulouse III) , University Hospital (UHC) of Toulouse, Toulouse, France;

关键词: endothelium;    shear stress;    estrogen receptors;    blood flow;    resistance arteries;    Mouse;   

DOI  :  10.7554/eLife.68695

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY