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.
Highlights
Polycystic ovary syndrome (PCOS) occurs in 6–20% of reproductive aged women [1,2]
Patients with homeostatic model assessment (HOMA)-Insulin resistance (IR)>2.5 exhibited a significant increase in diastolic BP, total cholesterol, low density lipoproteins cholesterol (LDLc), triglycerides, high sensitivity c-reactive protein (hsCRP), insulin, testosterone and androstendione (p
No changes were detected in the biochemical parameters of any of the PCOS groups according to homeostatic model assessment of IR (HOMA-IR), exception of triglycerides and insulin (p
Summary
Polycystic ovary syndrome (PCOS) occurs in 6–20% of reproductive aged women [1,2]. Insulin resistance (IR) is related to PCOS [3], and metabolic syndrome is reported in PCOS patients, increasing the risk of major cardiovascular events, morbidity and diabetes and affecting patient quality of life and overall health care costs [4,5,6].Inflammation and oxidative stress have been related to the pathogenesis of PCOS [7,8], including an increase in reactive oxygen species (ROS) production by peripheral blood leukocytes [9,10], activation of leukocyte-endothelium interactions [11] and the proinflammatory transcription factor nuclear κβ (NF-κβ), and a rise in the levels of proinflammatory cytokines [12] and C-reactive proteins [13]. Oxidative stress has been implicated in the etiology of IR in leukocytes from PCOS patients, and an increase in leukocytes has been highlighted as a putative marker of low-grade chronic inflammation and early cardiovascular risk in these subjects [13]. In this sense, it has been suggested that some enzymes, such as myeloperoxidase (MPO), a heme protein derived from leukocytes, play an important role in leukocyte-mediated endothelium damage in inflammation and cardiovascular diseases [14]. Several studies have explored the relationship between MPO and PCOS [16,17,18]
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