Metabolic syndrome enhances endoplasmic reticulum, oxidative stress and leukocyte-endothelium interactions in PCOS

Polycystic ovary syndrome (PCOS) is associated with insulin resistance, which can lead to metabolic syndrome (MetS). Oxidative stress and leukocyte-endothelium interactions are related to PCOS. Our aim was to evaluate whether the presence of MetS in PCOS patients can influence endoplasmic reticulum (ER) and oxidative stress and leukocyte-endothelium interactions.

This was a prospective controlled study conducted in an academic medical center. The study population consisted of 148 PCOS women (116 without/32 with MetS) and 112 control subjects (87 without / 25 with MetS). Metabolic parameters, reactive oxygen species (ROS) production, ER stress markers (GRP78, sXBP1, ATF6), leukocyte-endothelium interactions, adhesion molecules (VCAM-1, ICAM-1, E-Selectin), TNF-α and IL-6 were determined.

Total ROS, inflammatory parameters and adhesion molecules were enhanced in the presence of MetS (p<0.05), and the PCOS+MetS group showed higher levels of IL-6 and ICAM-1 than controls (p<0.05). Increased adhesion and leukocyte rolling flux were observed in PCOS and PCOS+MetS groups vs their respective controls (p<0.05). GRP78 protein expression was higher in the PCOS groups (p<0.05 vs controls) and sXBP1 was associated with the presence of MetS (p<0.05 vs controls without MetS). Furthermore, PCOS+MetS patients exhibited higher GRP78 and ATF6 levels than controls and PCOS patients without MetS (p<0.05). In PCOS women, HOMA-IR was positively correlated with ICAM-1 (r=0.501; p<0.01), ROS (r=0.604; p<0.01), rolling flux (r=0.455;p<0.05) and GRP78 (r=0.574; p<0.001).

Our findings support the hypothesis of an association between altered metabolic status, increased ROS production, ER stress and leukocyte-endothelium interactions in PCOS, all of which are related to vascular complications.