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Ruolo di GPER sulla funzione cardiovascolare in condizioni di ipertensione: caratterizzazione fisiologica del recettore in Ratti Spontaneamente ipertesi (SHR)

dc.contributor.authorDe Francesco, Ernestina Marianna
dc.contributor.authorMaggiolini, Marcello
dc.contributor.authorAngelone, Tommaso
dc.date.accessioned2016-03-03T11:13:58Z
dc.date.available2016-03-03T11:13:58Z
dc.date.issued2013-11-25
dc.identifier.urihttp://hdl.handle.net/10955/791
dc.identifier.urihttp://dx.doi.org/10.13126/UNICAL.IT/DOTTORATI/791
dc.descriptionDottorato di ricerca in Biologia animle, Ciclo XXVI, a.a. 2012-2013en_US
dc.description.abstractEstrogens 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 G-15 and the eNOS inhibitor L-NIO. Similarly, the G-1 induced activation of ERK1/2, AKT, GSK3β, c-Jun and eNOS was abrogated by G-15, 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, G-15 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.en_US
dc.description.sponsorshipUniversità della Calabriaen_US
dc.language.isoiten_US
dc.relation.ispartofseriesBIO/09;
dc.subjectFisiologia animaleen_US
dc.subjectApparato circolatorioen_US
dc.subjectRattien_US
dc.subjectIpertensioneen_US
dc.subjectIpossiaen_US
dc.titleRuolo di GPER sulla funzione cardiovascolare in condizioni di ipertensione: caratterizzazione fisiologica del recettore in Ratti Spontaneamente ipertesi (SHR)en_US
dc.typeThesisen_US


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