المؤلفون: Favre, Julie, Vessieres, Emilie, Guihot, Anne-Laure, Grimaud, Linda, Proux, Coralyne, Loufrani, Laurent, Lenfant, Françoise, Fontaine, Coralie, Arnal, Jean-François, Henrion, Daniel

المصدر: International Journal of Molecular Sciences; Mar2022, Vol. 23 Issue 5, p2862, 1p

مصطلحات موضوعية: VASCULAR resistance, ESTROGEN receptors, ENDOTHELIUM diseases, SUPEROXIDE dismutase, MESENTERIC artery, OXIDATIVE stress

مستخلص: Flow-mediated dilation (FMD) of resistance arteries is essential for tissue perfusion but it decreases with ageing. As estrogen receptor alpha (Erα encoded by Esr1), and more precisely membrane ERα, plays an important role in FMD in young mice in a ligand-independent fashion, we evaluated its influence on this arteriolar function in ageing. We first confirmed that in young (6-month-old) mice, FMD of mesenteric resistance arteries was reduced in Esr1−/− (lacking ERα) and C451A-ERα (lacking membrane ERα). In old (24-month-old) mice, FMD was reduced in WT mice compared to young mice, whereas it was not further decreased in Esr1−/− and C451A-ERα mice. Markers of oxidative stress were similarly increased in old WT and C451A-ERα mice. Reduction in oxidative stress with superoxide dismutase plus catalase or Mito-tempo, which reduces mitochondrial superoxide restored FMD to a normal control level in young C451A-ERα mice as well as in old WT mice and old C451A-ERα mice. Estradiol-mediated dilation was absent in old WT mice. We conclude that oxidative stress is a key event in the decline of FMD, and that an early defect in membrane ERα recapitulates phenotypically and functionally ageing of these resistance arteries. The loss of this function could take part in vascular ageing. [ABSTRACT FROM AUTHOR]

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المؤلفون: Favre, Julie¹, Vessieres, Emilie^1,2, Guihot, Anne- Laure^1,2, Proux, Coralyne^1,2, Grimaud, Linda¹, Rivron, Jordan^1,2, Garcia, Manuela CL^1,2, Réthoré, Léa¹, Zahreddine, Rana³, Davezac, Morgane³, Fébrissy, Chanaelle³, Adlanmerini, Marine³, Loufrani, Laurent^1,4, Procaccio, Vincent^1,4, Foidart, Jean- Michel⁵, Flouriot, Gilles⁶, Lenfant, Françoise³, Fontaine, Coralie³, Arnal, Jean- François³, Henrion, Daniel^1,2,4 daniel.henrion@univ-angers.fr

المصدر: eLife. 12/16/2021, p1-28. 28p.

مصطلحات موضوعية: *ESTROGEN receptors, *VASCULAR resistance, *OXIDATIVE stress, *ATHEROSCLEROTIC plaque, *ACETYLCHOLINE

مستخلص: 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 manne [ABSTRACT FROM AUTHOR]