title: Metformin modulates human leukocyte/endothelial cell interactions and proinflammatory cytokines in polycystic ovary syndrome patients.
abstract: OBJECTIVE
  We aim to assess the effect of metformin treatment on metabolic parameters, endothelial function and inflammatory markers in polycystic ovary syndrome (PCOS) subjects.
  
  
  METHODS
  The study population consisted of 40 reproductive-age women with PCOS, who underwent treatment with metformin during a 12-week period, and their corresponding matched controls (n = 44). We evaluated endocrinological parameters, adhesion molecules (vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule 1 (ICAM-1) and E-selectin) and proinflammatory cytokines (interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα)) in serum. In addition, interactions between human umbilical vein endothelial cells and polymorphonuclear (PMN) cells were assessed by flow chamber microscopy. In addition, a group of type 2 diabetes patients who underwent treatment with metformin during a 12-week period was incorporated into the study.
  
  
  RESULTS
  Metformin produced beneficial effects on PCOS patients by decreasing polymorphonuclear (PMN) rolling flux and adhesion. It also decreased levels of ICAM-1, E-selectin, IL-6 and ΤΝFα. In addition, metformin induced an improvement of endocrine and anthropometric parameters in PCOS subjects by reducing glucose, follicle-stimulating hormone (FSH) and androstendione, and by increasing dehydroepiandrosterone-sulfate (DHEA-S). Metformin also had beneficial effects in type 2 diabetic subjects by reducing body weight, waist circumference and PMN adhesion, and by increasing PMN rolling velocity.
  
  
  CONCLUSIONS
  Our results highlight the modulating effect of metformin on leukocyte/endothelium interactions. These findings may explain the potential beneficial effect of metformin in reducing the risk of vascular events in PCOS patients and in insulin resistance conditions.
authors.affiliation: Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain; Department of Physiology, University of Valencia, Valencia, Spain; Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Spain. Electronic address: Victor.Victor@uv.es.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Victor
authors.affiliation: Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Rovira-Llopis
authors.affiliation: Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Bañuls
authors.affiliation: Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Diaz-Morales
authors.affiliation: Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lopez-Domenech
authors.affiliation: Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Escribano-López
authors.affiliation: Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Spain.
authors.forename: Cesar
authors.initials: C
authors.lastname: Rios-Navarro
authors.affiliation: Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Spain; Fundación General de Universidad de Valencia, Valencia, Spain.
authors.forename: Angeles
authors.initials: A
authors.lastname: Alvarez
authors.affiliation: Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain.
authors.forename: Marcelino
authors.initials: M
authors.lastname: Gomez
authors.affiliation: Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain; Department of Pharmacology and CIBERehd, Faculty of Medicine, University of Valencia, Spain. Electronic address: Milagros.Rocha@uv.es.
authors.forename: Milagros
authors.initials: M
authors.lastname: Rocha
authors.affiliation: Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain. Electronic address: hernandez_antmij@gva.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Hernandez-Mijares
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000097:blood*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D036904:Leukocyte Rolling / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D018836:Inflammation Mediators; D008687:Metformin
keywords: Endothelium; Leukocyte; Metformin; Mitochondria; PCOS; Type 2 diabetes