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.

Immunophenotypic Profiles in Polycystic Ovary Syndrome

“…The white blood cell counts in the peripheral blood of patients with PCOS and hyperinsulinemia increased along with hyperandrogen production [91] and mainly increased in macrophages and neutrophils, which infiltrate this excessive fat to "clean up" dysfunctional and dead cells, resulting in a state of chronic low-grade inflammation [11]. As PCOS is usually treated with oral contraceptive and metformin [92], the number of macrophages and neutrophils may become even higher under treatment with oral contraceptive monotherapy and could be improved with metformin [91]. Besides its better-known effects in the improvement of oxidative stress and insulin resistance, metformin is also an effective treatment for immune-related disorders.…”

Obesity impairs leukocyte‐endothelium cell interactions and oxidative stress in humans

“…20 Percentage of A1c was measured with an automatic glycohemoglobin analyzer (Arkray Inc., Kyoto, Japan), and high-sensitive C-reactive protein (hsCRP) levels were quantified by an immunonephelometric assay. Levels of glucose, total cholesterol (TC) and triglycerides (TG) in serum were determined by means of an enzymatic method.…”

“…Obese patients were classified as IR obese when the HOMA index was >2.5 and non-IR obese when the HOMA index was <2.5, as in a previously published study. 20 Percentage of A1c was measured with an automatic glycohemoglobin analyzer (Arkray Inc., Kyoto, Japan), and high-sensitive C-reactive protein (hsCRP) levels were quantified by an immunonephelometric assay.…”

Effect of Hawthorn Leaf Flavonoids in Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome in Rats

“…For instance, Victor et al [27] showed that IR in PCOS patients enhanced oxidative stress and leukocyte adhesion. Kocer et al [28] demonstrated that metformin improved PCOS, probably by decreasing oxidative stress and improving IR.…”