Nuclear Activation Function 2 Estrogen Receptor α Attenuates Arterial and Renal Alterations Due to Aging and Hypertension in Female Mice - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of the American Heart Association Année : 2020

Nuclear Activation Function 2 Estrogen Receptor α Attenuates Arterial and Renal Alterations Due to Aging and Hypertension in Female Mice

(1) , , , , , , , , (1) , , , , , ,
1
Julie Favre
  • Fonction : Auteur
Anne-Laure Guihot
  • Fonction : Auteur
Emilie Vessières
  • Fonction : Auteur
Linda Grimaud
  • Fonction : Auteur
Coralyne Proux
  • Fonction : Auteur
Jordan Rivron
  • Fonction : Auteur
Agnès Barbelivien
  • Fonction : Auteur
Marie Briet
  • Fonction : Auteur
Françoise Lenfant
  • Fonction : Auteur
Coralie Fontaine
  • Fonction : Auteur
Laurent Loufrani
Jean‐françois Arnal
  • Fonction : Auteur
Daniel Henrion

Résumé

Background The cardiovascular protective effects of estrogens in premenopausal women depend mainly on estrogen receptor α (ERα). ERα activates nuclear gene transcription regulation and membrane‐initiated signaling. The latter plays a key role in estrogen‐dependent activation of endothelial NO synthase. The goal of the present work was to determine the respective roles of the 2 ERα activities in endothelial function and cardiac and kidney damage in young and old female mice with hypertension, which is a major risk factor in postmenopausal women. Methods and Results Five‐ and 18‐month‐old female mice lacking either ERα (ERα−/−), the nuclear activating function AF2 of ERα (AF2°), or membrane‐located ERα (C451A) were treated with angiotensin II (0.5 mg/kg per day) for 1 month. Systolic blood pressure, left ventricle weight, vascular reactivity, and kidney function were then assessed. Angiotensin II increased systolic blood pressure, ventricle weight, and vascular contractility in ERα−/− and AF2° mice more than in wild‐type and C451A mice, independent of age. In both the aorta and mesenteric resistance arteries, angiotensin II and aging reduced endothelium‐dependent relaxation in all groups, but this effect was more pronounced in ERα−/− and AF2° than in the wild‐type and C451A mice. Kidney inflammation and oxidative stress, as well as blood urea and creatinine levels, were also more pronounced in old hypertensive ERα−/− and AF2° than in old hypertensive wild‐type and C451A mice. Conclusions The nuclear ERα‐AF2 dependent function attenuates angiotensin II–dependent hypertension and protects target organs in aging mice, whereas membrane ERα signaling does not seem to play a role.
Fichier principal
Vignette du fichier
JAHA.119.013895.pdf (13.87 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03101944 , version 1 (08-01-2021)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification - CC BY 4.0

Identifiants

Citer

Emmanuel Guivarc'H, Julie Favre, Anne-Laure Guihot, Emilie Vessières, Linda Grimaud, et al.. Nuclear Activation Function 2 Estrogen Receptor α Attenuates Arterial and Renal Alterations Due to Aging and Hypertension in Female Mice. Journal of the American Heart Association, 2020, 9 (5), ⟨10.1161/JAHA.119.013895⟩. ⟨hal-03101944⟩
28 Consultations
50 Téléchargements

Altmetric

Partager

Gmail Facebook Twitter LinkedIn More