title: MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors.
abstract: OBJECTIVE
  Could an aberrant microRNA (miRNA) expression profile be responsible for the changes in the angiogenic and fibrinolytic states observed in endometriotic lesions?
  
  
  CONCLUSIONS
  This study revealed characteristic miRNA expression profiles associated with endometriosis in endometrial tissue and endometriotic lesions from the same patient and their correlation with the most important angiogenic and fibrinolytic factors. WHAT IS ALREADY KNOWN?: An important role for dysregulated miRNA expression in the pathogenesis of endometriosis is well documented. However, to the best of our knowledge, there are no reports of the relationship between angiogenic and fibrinolytic factors and miRNAs when endometrial tissue and different types of endometriotic lesions from the same patient are compared.
  
  
  METHODS
  Case-control study that involved 51 women with endometriosis and 32 women without the disease (controls).
  
  
  METHODS
  The miRNA expression profiles were determined using the GeneChip miRNA 2.0 Affymetrix array platform, and the results were analysed using Partek Genomic Suite software. To validate the obtained results, 12 miRNAs differentially expressed were quantified by using miRCURY LNA™ Universal RT microRNA PCR. Levels of vascular endothelial growth factor (VEGF-A), thrombospondin-1 (TSP-1), urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) proteins were quantified by ELISA.
  
  
  RESULTS
  Patient endometrial tissue showed significantly lower levels of miR-202-3p, miR-424-5p, miR-449b-3p and miR-556-3p, and higher levels of VEGF-A and uPA than healthy (control) endometrium. However, tissue affected by ovarian endometrioma showed significantly lower expression of miR-449b-3p than endometrium from both controls and patients, and higher levels of PAI-1 and the angiogenic inhibitor TSP-1. A significant inverse correlation between miR-424-5p and VEGF-A protein levels was observed in patient endometrium, and an inverse correlation between miR-449b-3p and TSP-1 protein levels was observed in ovarian endometrioma. Peritoneal implants had significantly higher levels of VEGF-A than ovarian endometrioma samples.
  
  
  CONCLUSIONS
  Functional studies are needed to confirm the specific targets of the miRNAs differently expressed.
  
  
  CONCLUSIONS
  Differences in miRNA levels could modulate the expression of VEGF-A and TSP-1, which may play an important role in the pathogenesis of endometriosis. The higher angiogenic and proteolytic activities observed in eutopic endometrium from patients might facilitate the implantation of endometrial cells at ectopic sites.
  
  
  BACKGROUND
  This work was supported by research grants from ISCIII-FEDER (PI11/0091, Red RIC RD12/0042/0029), Consellería de Educación-Generalitat Valenciana (PROMETEO/2011/027), Beca de Investigación Fundación Dexeus para la Salud de la Mujer (2011/0469), and by Fundación Investigación Hospital La Fe (2011/211). A.B-B. has a Contrato Posdoctoral de Perfeccionamiento Sara Borrell-ISCIII (CD13/00005). J.M-A. has a predoctoral grant PFIS-ISCIII (FI12/00012). The authors have no conﬂicts of interest to declare.
authors.affiliation: Grupo de Hemostasia, Trombosis, Arteriosclerosis y Biología Vascular, Instituto Investigación Sanitaria Hospital La Fe (IIS La Fe), Valencia, Spain.
authors.forename: Aitana
authors.initials: A
authors.lastname: Braza-Boïls
authors.forename: Josep
authors.initials: J
authors.lastname: Marí-Alexandre
authors.forename: Juan
authors.initials: J
authors.lastname: Gilabert
authors.forename: Dolors
authors.initials: D
authors.lastname: Sánchez-Izquierdo
authors.forename: Francisco
authors.initials: F
authors.lastname: España
authors.forename: Amparo
authors.initials: A
authors.lastname: Estellés
authors.forename: Juan
authors.initials: J
authors.lastname: Gilabert-Estellés
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D014568:Urokinase-Type Plasminogen Activator
keywords: VEGF-A; angiogenesis; endometriosis; fibrinolysis; microRNA