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

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

2021

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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