| First Author | Favre J | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 34842136 | Mgi Jnum | J:329044 |
| Mgi Id | MGI:6836594 | Doi | 10.7554/eLife.68695 |
| Citation | Favre J, et al. (2021) Membrane estrogen receptor alpha (ERalpha) participates in flow-mediated dilation in a ligand-independent manner. Elife 10:e68695 |
| abstractText | Estrogen receptor alpha (ERalpha) activation by estrogens prevents atheroma through its nuclear action, whereas plasma membrane-located ERalpha accelerates endothelial healing. The genetic deficiency of ERalpha was associated with a reduction in flow-mediated dilation (FMD) in one man. Here, we evaluated ex vivo the role of ERalpha on FMD of resistance arteries. FMD, but not agonist (acetylcholine, insulin)-mediated dilation, was reduced in male and female mice lacking ERalpha (Esr1-/- mice) compared to wild-type mice and was not dependent on the presence of estrogens. In C451A-ERalpha mice lacking membrane ERalpha, not in mice lacking AF2-dependent nuclear ERalpha actions, FMD was reduced, and restored by antioxidant treatments. Compared to wild-type mice, isolated perfused kidneys of C451A-ERalpha mice revealed a decreased flow-mediated nitrate production and an increased H2O2 production. Thus, endothelial membrane ERalpha promotes NO bioavailability through inhibition of oxidative stress and thereby participates in FMD in a ligand-independent manner. |
