Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase

• Published in: PloS one Vol. 11; no. 3; p. e0151960
• Main Authors: Victor, Victor M., Rovira-Llopis, Susana, Bañuls, Celia, Diaz-Morales, Noelia, Martinez de Marañon, Arantxa, Rios-Navarro, Cesar, Alvarez, Angeles, Gomez, Marcelino, Rocha, Milagros, Hernández-Mijares, Antonio
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.03.2016; Public Library of Science (PLoS)
• Subjects: Adhesion; Adult; Age; Analysis; Anthropometry; Atherosclerosis; Biology and Life Sciences; Biomedical research; Cardiovascular disease; Cardiovascular diseases; Cell activation; Cell Adhesion; Cell adhesion molecules; Cytokines; Cytokines - metabolism; Diabetes; Diagnosis; E-selectin; Endocrinology; Endothelial cells; Endothelium; Female; Health care facilities; Heart diseases; Hospitals; Humans; Inflammation; Inflammation Mediators - metabolism; Insulin; Insulin Resistance; Intercellular adhesion molecule 1; Interleukin 6; Kinases; Leukocyte rolling; Leukocytes; Leukocytes - cytology; Medical research; Medicine and Health Sciences; Metabolic syndrome; Mitochondria; Mitochondria - metabolism; Oxidation resistance; Oxidative Stress; Oxygen; Patients; Peroxidase; Peroxidase - metabolism; Pharmacology; Physiological aspects; Physiology; Polycystic ovary syndrome; Polycystic Ovary Syndrome - metabolism; Polycystic Ovary Syndrome - pathology; Polycystic Ovary Syndrome - physiopathology; Population studies; Reactive oxygen species; Reactive Oxygen Species - metabolism; Research and Analysis Methods; Risk factors; Tumor necrosis factor-α; Umbilical vein; Vascular cell adhesion molecule 1; White blood cells; Womens health; Young Adult; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0151960

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.