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:	Ernestina Marianna De Francesco, Tommaso Angelone, Teresa Pasqua, Marco Pupo, Maria Carmela Cerra, Marcello Maggiolini
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e63281fd0ecc4beab045934cc636dc9b
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spelling	oai:doaj.org-article:e63281fd0ecc4beab045934cc636dc9b2021-11-18T09:00:30ZGPER mediates cardiotropic effects in spontaneously hypertensive rat hearts.1932-620310.1371/journal.pone.0069322https://doaj.org/article/e63281fd0ecc4beab045934cc636dc9b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23950890/?tool=EBIhttps://doaj.org/toc/1932-6203Estrogens 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.Ernestina Marianna De FrancescoTommaso AngeloneTeresa PasquaMarco PupoMaria Carmela CerraMarcello MaggioliniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e69322 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ernestina Marianna De Francesco Tommaso Angelone Teresa Pasqua Marco Pupo Maria Carmela Cerra Marcello Maggiolini GPER mediates cardiotropic effects in spontaneously hypertensive rat hearts.
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.
format	article
author	Ernestina Marianna De Francesco Tommaso Angelone Teresa Pasqua Marco Pupo Maria Carmela Cerra Marcello Maggiolini
author_facet	Ernestina Marianna De Francesco Tommaso Angelone Teresa Pasqua Marco Pupo Maria Carmela Cerra Marcello Maggiolini
author_sort	Ernestina Marianna De Francesco
title	GPER mediates cardiotropic effects in spontaneously hypertensive rat hearts.
title_short	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_sort	gper mediates cardiotropic effects in spontaneously hypertensive rat hearts.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e63281fd0ecc4beab045934cc636dc9b
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GPER mediates cardiotropic effects in spontaneously hypertensive rat hearts.

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