Estrogen rescues heart failure through estrogen receptor Beta activation

Andrea Iorga, Soban Umar, Gregoire Ruffenach, Laila Aryan, Jingyuan Li, Salil Sharma, Negar Motayagheni, Rangarajan D. Nadadur, Jean C Bopassa, Mansoureh Eghbali

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: Recently, we showed that exogenous treatment with estrogen (E2) rescues pre-existing advanced heart failure (HF) in mice. Since most of the biological actions of E2 are mediated through the classical estrogen receptors alpha (ERα) and/or beta (ERβ), and both these receptors are present in the heart, we examined the role of ERα and ERβ in the rescue action of E2 against HF. Methods: Severe HF was induced in male mice by transverse aortic constriction-induced pressure overload. Once the ejection fraction (EF) reached ~ 35%, mice were treated with selective agonists for ERα (PPT, 850 μg/kg/day), ERβ (DPN, 850 μg/kg/day), or E2 (30 μg/kg/day) together with an ERβ-antagonist (PHTPP, 850 μg/kg/day) for 10 days. Results: EF of HF mice was significantly improved to 45.3 ± 2.1% with diarylpropionitrile (DPN) treatment, but not with PPT (31.1 ± 2.3%). E2 failed to rescue HF in the presence of PHTPP, as there was no significant improvement in the EF at the end of the 10-day treatment (32.5 ± 5.2%). The improvement of heart function in HF mice treated with ERβ agonist DPN was also associated with reduced cardiac fibrosis and increased cardiac angiogenesis, while the ERα agonist PPT had no significant effect on either cardiac fibrosis or angiogenesis. Furthermore, DPN improved hemodynamic parameters in HF mice, whereas PPT had no significant effect. Conclusions: E2 treatment rescues pre-existing severe HF mainly through ERβ. Rescue of HF by ERβ activation is also associated with stimulation of cardiac angiogenesis, suppression of fibrosis, and restoration of hemodynamic parameters.

Original languageEnglish (US)
Article number48
JournalBiology of Sex Differences
Volume9
Issue number1
DOIs
StatePublished - Oct 30 2018

    Fingerprint

Keywords

  • Angiogenesis
  • Estrogen
  • Estrogen receptor alpha
  • Estrogen receptor Beta
  • Fibrosis
  • Heart failure

ASJC Scopus subject areas

  • Gender Studies
  • Endocrinology

Cite this

Iorga, A., Umar, S., Ruffenach, G., Aryan, L., Li, J., Sharma, S., Motayagheni, N., Nadadur, R. D., Bopassa, J. C., & Eghbali, M. (2018). Estrogen rescues heart failure through estrogen receptor Beta activation. Biology of Sex Differences, 9(1), [48]. https://doi.org/10.1186/s13293-018-0206-6