Estradiol, acting through ERα, induces endothelial non-classic renin-angiotensin system increasing angiotensin 1-7 production.

MOMPEÓN A, LÁZARO-FRANCO M, BUENO-BETÍ C, PÉREZ-CREMADES D, VIDAL-GÓMEZ X, MONSALVE E, GIRONACCI MM, HERMENEGILDO C, NOVELLA S.

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2016 vol. 422 p. 1 - 8

0303-7207

Intracellular renin-angiotensin system (RAS) can operate independently of the circulating RAS. Estrogensprovide protective effects by modulating the RAS. Our aim was to investigate the effect of estradiol (E2)on angiotensin converting enzymes (ACE) 1 and ACE2 expression and activities in human endothelialcells (HUVEC), and the role of estrogen receptors (ER). The results confirmed the presence of active intracellular RAS in HUVEC. Physiological concentrations of E2 induced a concentration-dependent increase of ACE1 and ACE2 mRNA expression and ACE1, but not ACE2, protein levels. ACE1 and ACE2 enzymatic activities were also induced with E2. These effects were mediated through ERa activation, since ER antagonists ICI 182780 and MPP completely abolished the effect of E2. Moreover, the ERa agonist PPT mirrored the E2 effects on ACE1 and ACE2 protein expression and activity. Exposure of endothelial cells to E2 Significantly increased Ang-(1e7) production. In conclusion, E2 increases Ang-(1e7) production,through ERa, involving increased ACE1 and ACE2 mRNA expression and activity and ACE1 protein levels.