title: Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase.
abstract: Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR<2.5) and PCOS IR (HOMA-IR>2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (ROS) production, MPO levels, interactions between human umbilical vein endothelial cells and leukocytes, adhesion molecules (E-selectin, ICAM-1 and VCAM-1) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. Oxidative stress was observed in PCOS patients, in whom there was an increase in total and mitochondrial ROS production and MPO levels. Enhanced rolling flux and adhesion, and a decrease in polymorphonuclear cell rolling velocity were also detected in PCOS subjects. Increases in IL-6 and TNF-α and adhesion molecules (E-selectin, ICAM-1 and VCAM-1) were also observed, particularly in the PCOS IR group, providing evidence that inflammation and oxidative stress are related in PCOS patients. HOMA-IR was positively correlated with hsCRP (p<0.001, r = 0.304), ROS production (p<0.01, r = 0.593), leukocyte rolling flux (p<0.05, r = 0.446), E-selectin (p<0.01, r = 0.436) and IL-6 (p<0.001, r = 0.443). The results show an increase in the rate of ROS and MPO levels in PCOS patients in general, and particularly in those with IR. Inflammation in PCOS induces leukocyte-endothelium interactions and a simultaneous increase in IL-6, TNF-α, E-selectin, ICAM-1 and VCAM-1. These conditions are aggravated by the presence of IR.
authors.affiliation: Service of Endocrinology, University Hospital Doctor 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.|CIBERehd - Department of Pharmacology and Physiology, University of Valencia, Valencia, Spain.|Department of Physiology, University of Valencia, Valencia, Spain.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Victor
authors.affiliation: Service of Endocrinology, University Hospital Doctor 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 Doctor 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 Doctor 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 Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
authors.forename: Arantxa
authors.initials: A
authors.lastname: Martinez de Marañon
authors.affiliation: CIBERehd - Department of Pharmacology and Physiology, University of Valencia, Valencia, Spain.
authors.forename: Cesar
authors.initials: C
authors.lastname: Rios-Navarro
authors.affiliation: CIBERehd - Department of Pharmacology and Physiology, University of Valencia, Valencia, Spain.|General Foundation of the University of Valencia, Valencia, Spain.
authors.forename: Angeles
authors.initials: A
authors.lastname: Alvarez
authors.affiliation: Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
authors.forename: Marcelino
authors.initials: M
authors.lastname: Gomez
authors.affiliation: Service of Endocrinology, University Hospital Doctor 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.|CIBERehd - Department of Pharmacology and Physiology, University of Valencia, Valencia, Spain.
authors.forename: Milagros
authors.initials: M
authors.lastname: Rocha
authors.affiliation: Service of Endocrinology, University Hospital Doctor 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.
authors.forename: Antonio
authors.initials: A
authors.lastname: Hernández-Mijares
mesh_terms: D000328:Adult; D002448:Cell Adhesion; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D007962:Leukocytes / Q000166:cytology*; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D009195:Peroxidase