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Artículo

Regulatory effects of estetrol on the endothelial plasminogen pathway and endothelial cell migration

Montt Guevara, Maria MagdalenaIcon ; Palla, Giulia; Spina, Stefania; Bernacchi, Guja; Cecchi, Elena; Campelo, Adrián EstebanIcon ; Shortrede, Jorge Eduardo; Canu, Alessio; Simoncini, Tommaso
Fecha de publicación: 05/2017
Editorial: Elsevier Ireland
Revista: Maturitas
ISSN: 0378-5122
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Salud Ocupacional

Resumen

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.
Palabras clave: Estetrol , Estrogen , Huvec , Pai-1 , T-Pa , U-Pa
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/57349
DOI: http://dx.doi.org/10.1016/j.maturitas.2017.02.005
URL: https://www.sciencedirect.com/science/article/pii/S0378512216303905
Colecciones
Articulos(INBIOSUR)
Articulos de INSTITUTO DE CIENCIAS BIOLOGICAS Y BIOMEDICAS DEL SUR
Citación
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
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