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Estrogen rescues heart failure through estrogen receptor Beta activation

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 i...

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Autores principales: Iorga, Andrea, Umar, Soban, Ruffenach, Gregoire, Aryan, Laila, Li, Jingyuan, Sharma, Salil, Motayagheni, Negar, Nadadur, Rangarajan D., Bopassa, Jean C., Eghbali, Mansoureh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208048/
https://www.ncbi.nlm.nih.gov/pubmed/30376877
http://dx.doi.org/10.1186/s13293-018-0206-6
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author Iorga, Andrea
Umar, Soban
Ruffenach, Gregoire
Aryan, Laila
Li, Jingyuan
Sharma, Salil
Motayagheni, Negar
Nadadur, Rangarajan D.
Bopassa, Jean C.
Eghbali, Mansoureh
author_facet Iorga, Andrea
Umar, Soban
Ruffenach, Gregoire
Aryan, Laila
Li, Jingyuan
Sharma, Salil
Motayagheni, Negar
Nadadur, Rangarajan D.
Bopassa, Jean C.
Eghbali, Mansoureh
author_sort Iorga, Andrea
collection PubMed
description 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.
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spelling pubmed-62080482018-11-16 Estrogen rescues heart failure through estrogen receptor Beta activation Iorga, Andrea Umar, Soban Ruffenach, Gregoire Aryan, Laila Li, Jingyuan Sharma, Salil Motayagheni, Negar Nadadur, Rangarajan D. Bopassa, Jean C. Eghbali, Mansoureh Biol Sex Differ Research 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. BioMed Central 2018-10-30 /pmc/articles/PMC6208048/ /pubmed/30376877 http://dx.doi.org/10.1186/s13293-018-0206-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Iorga, Andrea
Umar, Soban
Ruffenach, Gregoire
Aryan, Laila
Li, Jingyuan
Sharma, Salil
Motayagheni, Negar
Nadadur, Rangarajan D.
Bopassa, Jean C.
Eghbali, Mansoureh
Estrogen rescues heart failure through estrogen receptor Beta activation
title Estrogen rescues heart failure through estrogen receptor Beta activation
title_full Estrogen rescues heart failure through estrogen receptor Beta activation
title_fullStr Estrogen rescues heart failure through estrogen receptor Beta activation
title_full_unstemmed Estrogen rescues heart failure through estrogen receptor Beta activation
title_short Estrogen rescues heart failure through estrogen receptor Beta activation
title_sort estrogen rescues heart failure through estrogen receptor beta activation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208048/
https://www.ncbi.nlm.nih.gov/pubmed/30376877
http://dx.doi.org/10.1186/s13293-018-0206-6
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