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dc.contributor.authorArroyo, Ana Belen V.
dc.contributor.authorSalloum-Asfar, Salam
dc.contributor.authorPérez-Sánchez, Carlos
dc.contributor.authorTeruel-Montoya, Raúl
dc.contributor.authorNavarro, Silvia
dc.contributor.authorGarcía-Barberá, Nuria
dc.contributor.authorLuengo-Gil, Ginés
dc.contributor.authorRoldán, Vanessa
dc.contributor.authorHansen, John-Bjarne
dc.contributor.authorVicente, Vicente
dc.contributor.authorGónzález-Conejero, Rocío
dc.contributor.authorMartínez, Constantino
dc.date.accessioned2018-03-05T13:00:49Z
dc.date.available2018-03-05T13:00:49Z
dc.date.issued2017-02-27
dc.description.abstractThe increased risk of cardiovascular events in older men is multifactorial, but the significant reduction of testosterone levels has been involved. As this hormone regulates the expression of TFPI by unknown mechanisms, we aimed to evaluate the role of miRNAs in the regulation of TFPIα expression under normal conditions and in response to androgens. In silico studies allowed the selection of 4 miRNAs as potential TFPIα regulators. Only miR-27a/b-3p significantly reduced TFPIα expression in two endothelial cell lines. Luciferase assays demonstrated a direct interaction between miR-27a/b-3p and TFPI 3′UTR. Ex vivo analysis of TFPI and miRNA levels in 74 HUVEC samples from healthy subjects, showed a significant and inverse correlation between TFPI and miR-27a-3p. Moreover, anticoagulant activity of TFPIα from cells supernatants decreased ~30% with miR-27a/b-3p and increased ~50% with anti-miR-27a/b-3p. Interestingly, treatment of EA.hy926 with a physiological dose of dihydrotestosterone (30 nM) significantly increased (~40%) TFPIα expression with a parallel decreased (~50%) of miR-27a/b-3p expression. In concordance, increased levels of miR-27a/b-3p normalized the up-regulation induced by testosterone. Our results suggest that testosterone is a hinge in miR-27/TFPIα regulation axis. Future studies are needed to investigate whether testosterone variations are involved in a miR-27/TFPIα dysregulation that could increase the cardiovascular risk.en_US
dc.descriptionSource at <a href=https://doi.org/doi:10.1038/srep43500> https://doi.org/doi:10.1038/srep43500 </a>.en_US
dc.identifier.citationArroyo, A.B., Salloum-Asfar, S., Pérez-Sánchez, C., Teruel-Montoya, R., Navarro, S., García-Barberá, N. ... Martínez, C. (2017). Regulation of TFPIα expression by miR-27a/b-3p in human endothelial cells under normal conditions and in response to androgens. Scientific Reports. 7:43500.en_US
dc.identifier.cristinIDFRIDAID 1489828
dc.identifier.doi10.1038/srep43500
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/10037/12249
dc.language.isoengen_US
dc.publisherNature Publishing Groupen_US
dc.relation.journalScientific Reports
dc.relation.projectIDInstituto de Salud Carlos IIIen_US
dc.relation.projectIDFondo Europeo de Desarrollo Regional (FEDER)en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectMolecular medicineen_US
dc.subjectThrombosisen_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Kardiologi: 771en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Cardiology: 771en_US
dc.titleRegulation of TFPIα expression by miR-27a/b-3p in human endothelial cells under normal conditions and in response to androgensen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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