title: Induction of oxidative stress and human leukocyte/endothelial cell interactions in polycystic ovary syndrome patients with insulin resistance.
abstract: BACKGROUND
  Insulin resistance is a feature of polycystic ovary syndrome (PCOS) and is related to mitochondrial and endothelial function.
  
  
  OBJECTIVE
  We tested whether hyperandrogenic insulin-resistant women with PCOS, who have an increased risk of vascular disease, display impaired leukocyte-endothelium interactions, and mitochondrial dysfunction.
  
  
  METHODS
  This was a prospective controlled study conducted in an academic medical center.
  
  
  METHODS
  The study population consisted of 43 lean reproductive-age women with PCOS and 39 controls subjects.
  
  
  METHODS
  We evaluated anthropometric and metabolic parameters, adhesion molecules, and interactions between leukocytes and human umbilical vein endothelial cells. Mitochondrial function was studied by assessing mitochondrial oxygen consumption, membrane potential, reactive oxygen species production, glutathione levels (GSH), and the oxidized glutathione (GSSG)/GSH ratio in polymorphonuclear cells.
  
  
  RESULTS
  Impairment of mitochondrial function was observed in the PCOS patients, evident in a decrease in oxygen consumption, an increase in reactive oxygen species production, a decrease in the GSH/GSSG ratio and GSH levels, and an undermining of the membrane potential. PCOS was related to a decrease in polymorphonuclear cell rolling velocity and an increase in rolling flux and adhesion. Increases in IL-6 and TNFα and adhesion molecules (vascular cell adhesion molecule-1 and E-selectin) were also observed.
  
  
  CONCLUSIONS
  This study supports the hypothesis of an association between insulin resistance and an impaired endothelial and mitochondrial oxidative metabolism. The evidence obtained shows that the inflammatory state related to insulin resistance in PCOS induces a leukocyte-endothelium interaction. These findings may explain the increased risk of vascular disease in women with PCOS.
authors.affiliation: Endocrinology Service, University Hospital Doctor Peset, and University Hospital Doctor Peset Foundation, 46017 Valencia, Spain. victor.victor@uv.es
authors.forename: Victor M
authors.initials: VM
authors.lastname: Victor
authors.forename: Milagros
authors.initials: M
authors.lastname: Rocha
authors.forename: Celia
authors.initials: C
authors.lastname: Bañuls
authors.forename: Angeles
authors.initials: A
authors.lastname: Alvarez
authors.forename: Carmen
authors.initials: C
authors.lastname: de Pablo
authors.forename: Maria
authors.initials: M
authors.lastname: Sanchez-Serrano
authors.forename: Marcelino
authors.initials: M
authors.lastname: Gomez
authors.forename: Antonio
authors.initials: A
authors.lastname: Hernandez-Mijares
mesh_terms: D000293:Adolescent; D000328:Adult; D002469:Cell Separation; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology; D011085:Polycystic Ovary Syndrome / Q000473:pathology*; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D019040:E-Selectin; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D005978:Glutathione