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dc.contributor.author
Montt Guevara, Maria Magdalena
dc.contributor.author
Palla, Giulia
dc.contributor.author
Spina, Stefania
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Bernacchi, Guja
dc.contributor.author
Cecchi, Elena
dc.contributor.author
Campelo, Adrián Esteban
dc.contributor.author
Shortrede, Jorge Eduardo
dc.contributor.author
Canu, Alessio
dc.contributor.author
Simoncini, Tommaso
dc.date.available
2018-08-28T17:44:21Z
dc.date.issued
2017-05
dc.identifier.citation
Montt Guevara, Maria Magdalena; Palla, Giulia; Spina, Stefania; Bernacchi, Guja; Cecchi, Elena; et al.; Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration; Elsevier Ireland; Maturitas; 99; 5-2017; 1-9
dc.identifier.issn
0378-5122
dc.identifier.uri
http://hdl.handle.net/11336/57349
dc.description.abstract
BACKGROUND: Estetrol (E4) is a natural estrogen produced solely during human pregnancy. E4 is suitable for clinical use since it acts as a selective estrogen receptor modulator. In clinical trials E4 has been seen to have little or no effect on coagulation. Hence, it is interesting to investigate whether E4 alters endothelial-dependent fibrinolysis. OBJECTIVES: We studied the effects of E4 on the fibrinolytic system and whether this could influence the ability of endothelial cells to migrate. In addition, we compared the effects of E4 with those of 17β-estradiol (E2). STUDY DESIGN: Human umbilical vein endothelial cells (HUVEC) were obtained from healthy women. Expression of plasminogen-activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (u-PA) and tissue plasminogen activator (t-PA) proteins was evaluated by Western blot analysis. Endothelial cell migration was studied by razor-scrape horizontal and multiwell insert systems assays. RESULTS: E4 increased the expression of t-PA, u-PA and PAI-1 in HUVEC, but less so than did equimolar amounts of E2. The effects of E4 on t-PA, u-PA and PAI-1 were mediated by the induction of the early-immediate genes c-Jun and c-Fos. E4 in combination with E2 antagonized the effects induced by pregnancy-like E2 concentrations but did not impair the effects of postmenopausal-like E2 levels. We also found that the increased synthesis of PAI-1, u-PA and t-PA induced by E2 and E4 is important for horizontal and three-dimensional migration of HUVEC. CONCLUSIONS: These results support the hypothesis that E4 acts as an endogenous selective estrogen receptor modulator (SERM), controlling the fibrinolytic system and endothelial cell migration.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Ireland
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Estetrol
dc.subject
Estrogen
dc.subject
Huvec
dc.subject
Pai-1
dc.subject
T-Pa
dc.subject
U-Pa
dc.subject.classification
Salud Ocupacional
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-08-23T18:53:59Z
dc.journal.volume
99
dc.journal.pagination
1-9
dc.journal.pais
Irlanda
dc.journal.ciudad
Shannon
dc.description.fil
Fil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Università degli Studi di Pisa; Italia
dc.description.fil
Fil: Palla, Giulia. Università degli Studi di Pisa; Italia
dc.description.fil
Fil: Spina, Stefania. Università degli Studi di Pisa; Italia
dc.description.fil
Fil: Bernacchi, Guja. Università degli Studi di Pisa; Italia
dc.description.fil
Fil: Cecchi, Elena. Università degli Studi di Pisa; Italia
dc.description.fil
Fil: Campelo, Adrián Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina. Università degli Studi di Pisa; Italia
dc.description.fil
Fil: Shortrede, Jorge Eduardo. Università degli Studi di Pisa; Italia
dc.description.fil
Fil: Canu, Alessio. Università degli Studi di Pisa; Italia
dc.description.fil
Fil: Simoncini, Tommaso. Università degli Studi di Pisa; Italia
dc.journal.title
Maturitas
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.maturitas.2017.02.005
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0378512216303905
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