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

PLoS One. 2016 Mar 23;11(3):e0151960. doi: 10.1371/journal.pone.0151960. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Adhesion*
  • Cytokines / metabolism
  • Female
  • Humans
  • Inflammation Mediators / metabolism
  • Insulin Resistance*
  • Leukocytes / cytology*
  • Mitochondria / metabolism
  • Oxidative Stress*
  • Peroxidase / metabolism
  • Polycystic Ovary Syndrome / metabolism*
  • Polycystic Ovary Syndrome / pathology
  • Polycystic Ovary Syndrome / physiopathology
  • Reactive Oxygen Species / metabolism
  • Young Adult

Substances

  • Cytokines
  • Inflammation Mediators
  • Reactive Oxygen Species
  • Peroxidase

Grant support

This study was financed by grants PI12/1984, PI13/1025, PI13/0073, PI15/1424, CIBERehd CB06/04/0071, PROMETEOII2014/035, SAF2010/16030, UGP-14-93, UGP-14-95 and by the European Regional Development Fund (ERDF “A way to build Europe”). VMV and MR are recipients of contracts from the Ministry of Health of the Valencian Regional Government and Carlos III Health Institute (CES10/030 and CP10/0360, respectively). SR-L is the recipient of a predoctoral fellowship from Carlos III Health Institute (FI11/00637). CB is the recipient of a postdoctoral contract from Carlos III Health Institute (CD14/00043). ND-M is the recipient of a predoctoral contract from Carlos III Health Institute (FI14/00125). CR-N was supported by Conselleria de Educación, Cultura y Deporte (CPI-13-194). AA was supported by Ministerio de Ciencia e Innovación (Ramón y Cajal program RYC2005-002295 and I3 program).