title: Regulation of TFPIα expression by miR-27a/b-3p in human endothelial cells under normal conditions and in response to androgens.
abstract: The 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.
authors.affiliation: Centro Regional de Hemodonación, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: B Arroyo
authors.affiliation: Centro Regional de Hemodonación, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Salam
authors.initials: S
authors.lastname: Salloum-Asfar
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC). Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Sánchez
authors.affiliation: Centro Regional de Hemodonación, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Teruel-Montoya
authors.affiliation: Medical Research Institute, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Navarro
authors.affiliation: Centro Regional de Hemodonación, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: García-Barberá
authors.affiliation: Centro Regional de Hemodonación, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Ginés
authors.initials: G
authors.lastname: Luengo-Gil
authors.affiliation: Centro Regional de Hemodonación, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Roldán
authors.affiliation: K. G. Jebsen - Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: John-Bjarne
authors.initials: JB
authors.lastname: Hansen
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC). Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.
authors.forename: Chary
authors.initials: C
authors.lastname: López-Pedrera
authors.affiliation: Centro Regional de Hemodonación, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
authors.affiliation: Centro Regional de Hemodonación, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: González-Conejero
authors.affiliation: Centro Regional de Hemodonación, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Constantino
authors.initials: C
authors.lastname: Martínez
mesh_terms: D020413:3' Untranslated Regions; D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008074:Lipoproteins / Q000235:genetics* / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology
chemical_list: D020413:3' Untranslated Regions; D000728:Androgens; D008074:Lipoproteins; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C051928:lipoprotein-associated coagulation inhibitor; D013739:Testosterone