GPER Mediates Cardiotropic Effects in Spontaneously Hypertensive Rat Hearts

Estrogens promote beneficial effects in the cardiovascular system mainly through the estrogen receptor (ER)α and ERβ, which act as ligand-gated transcription factors. Recently, the G protein-coupled estrogen receptor (GPER) has been implicated in the estrogenic signaling in diverse tissues, includin...

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Autores principales: De Francesco, Ernestina Marianna, Angelone, Tommaso, Pasqua, Teresa, Pupo, Marco, Cerra, Maria Carmela, Maggiolini, Marcello
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739764/
https://www.ncbi.nlm.nih.gov/pubmed/23950890
http://dx.doi.org/10.1371/journal.pone.0069322
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author De Francesco, Ernestina Marianna
Angelone, Tommaso
Pasqua, Teresa
Pupo, Marco
Cerra, Maria Carmela
Maggiolini, Marcello
author_facet De Francesco, Ernestina Marianna
Angelone, Tommaso
Pasqua, Teresa
Pupo, Marco
Cerra, Maria Carmela
Maggiolini, Marcello
author_sort De Francesco, Ernestina Marianna
collection PubMed
description Estrogens promote beneficial effects in the cardiovascular system mainly through the estrogen receptor (ER)α and ERβ, which act as ligand-gated transcription factors. Recently, the G protein-coupled estrogen receptor (GPER) has been implicated in the estrogenic signaling in diverse tissues, including the cardiovascular system. In this study, we demonstrate that left ventricles of male Spontaneously Hypertensive Rats (SHR) express higher levels of GPER compared to normotensive Wistar Kyoto (WKY) rats. In addition, we show that the selective GPER agonist G-1 induces negative inotropic and lusitropic effects to a higher extent in isolated and Langendorff perfused hearts of male SHR compared to WKY rats. These cardiotropic effects elicited by G-1 involved the GPER/eNOS transduction signaling, as determined by using the GPER antagonist G15 and the eNOS inhibitor L-NIO. Similarly, the G-1 induced activation of ERK1/2, AKT, GSK3β, c-Jun and eNOS was abrogated by G15, while L-NIO prevented only the eNOS phosphorylation. In hypoxic Langendorff perfused WKY rat heart preparations, we also found an increased expression of GPER along with that of the hypoxic mediator HIF-1α and the fibrotic marker CTGF. Interestingly, G15 and L-NIO prevented the ability of G-1 to down-regulate the expression of both HIF-1α and CTGF, which were found expressed to a higher extent in SHR compared to WKY rat hearts. Collectively, the present study provides novel data into the potential role played by GPER in hypertensive disease on the basis of its involvement in myocardial inotropism and lusitropism as well as the expression of the apoptotic HIF-1α and fibrotic CTGF factors. Hence, GPER may be considered as a useful target in the treatment of some cardiac dysfunctions associated with stressful conditions like the essential hypertension.
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spelling pubmed-37397642013-08-15 GPER Mediates Cardiotropic Effects in Spontaneously Hypertensive Rat Hearts De Francesco, Ernestina Marianna Angelone, Tommaso Pasqua, Teresa Pupo, Marco Cerra, Maria Carmela Maggiolini, Marcello PLoS One Research Article Estrogens promote beneficial effects in the cardiovascular system mainly through the estrogen receptor (ER)α and ERβ, which act as ligand-gated transcription factors. Recently, the G protein-coupled estrogen receptor (GPER) has been implicated in the estrogenic signaling in diverse tissues, including the cardiovascular system. In this study, we demonstrate that left ventricles of male Spontaneously Hypertensive Rats (SHR) express higher levels of GPER compared to normotensive Wistar Kyoto (WKY) rats. In addition, we show that the selective GPER agonist G-1 induces negative inotropic and lusitropic effects to a higher extent in isolated and Langendorff perfused hearts of male SHR compared to WKY rats. These cardiotropic effects elicited by G-1 involved the GPER/eNOS transduction signaling, as determined by using the GPER antagonist G15 and the eNOS inhibitor L-NIO. Similarly, the G-1 induced activation of ERK1/2, AKT, GSK3β, c-Jun and eNOS was abrogated by G15, while L-NIO prevented only the eNOS phosphorylation. In hypoxic Langendorff perfused WKY rat heart preparations, we also found an increased expression of GPER along with that of the hypoxic mediator HIF-1α and the fibrotic marker CTGF. Interestingly, G15 and L-NIO prevented the ability of G-1 to down-regulate the expression of both HIF-1α and CTGF, which were found expressed to a higher extent in SHR compared to WKY rat hearts. Collectively, the present study provides novel data into the potential role played by GPER in hypertensive disease on the basis of its involvement in myocardial inotropism and lusitropism as well as the expression of the apoptotic HIF-1α and fibrotic CTGF factors. Hence, GPER may be considered as a useful target in the treatment of some cardiac dysfunctions associated with stressful conditions like the essential hypertension. Public Library of Science 2013-08-09 /pmc/articles/PMC3739764/ /pubmed/23950890 http://dx.doi.org/10.1371/journal.pone.0069322 Text en © 2013 De Francesco et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
De Francesco, Ernestina Marianna
Angelone, Tommaso
Pasqua, Teresa
Pupo, Marco
Cerra, Maria Carmela
Maggiolini, Marcello
GPER Mediates Cardiotropic Effects in Spontaneously Hypertensive Rat Hearts
title GPER Mediates Cardiotropic Effects in Spontaneously Hypertensive Rat Hearts
title_full GPER Mediates Cardiotropic Effects in Spontaneously Hypertensive Rat Hearts
title_fullStr GPER Mediates Cardiotropic Effects in Spontaneously Hypertensive Rat Hearts
title_full_unstemmed GPER Mediates Cardiotropic Effects in Spontaneously Hypertensive Rat Hearts
title_short GPER Mediates Cardiotropic Effects in Spontaneously Hypertensive Rat Hearts
title_sort gper mediates cardiotropic effects in spontaneously hypertensive rat hearts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739764/
https://www.ncbi.nlm.nih.gov/pubmed/23950890
http://dx.doi.org/10.1371/journal.pone.0069322
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