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

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Favre, Julie | Vessieres, Emilie | Guihot, Anne-Laure | Proux, Coralyne | Grimaud, Linda | Rivron, Jordan | Garcia, Manuela Cl | Réthoré, Léa | Zahreddine, Rana | Davezac, Morgane | Fébrissy, Chanaelle | Adlanmerini, Marine | Loufrani, Laurent | Procaccio, Vincent | Foidart, Jean-Marie | Flouriot, Gilles | Lenfant, Francoise | Fontaine, Coralie | Arnal, Jean-Françoise | Henrion, Daniel

Edité par CCSD ; eLife Sciences Publication -

International audience. 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 H 2 O 2 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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