Bañuls Celia, Rovira-Llopis Susana, Martinez de Marañon Aranzazu, Veses Silvia, Jover Ana, Gomez Marcelino, Rocha Milagros, Hernandez-Mijares Antonio, Victor Victor M
Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain.
Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
Metabolism. 2017 Jun;71:153-162. doi: 10.1016/j.metabol.2017.02.012. Epub 2017 Feb 27.
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.
多囊卵巢综合征（PCOS）与胰岛素抵抗相关，后者可导致代谢综合征（MetS）。氧化应激和白细胞-内皮细胞相互作用与PCOS有关。我们的目的是评估PCOS患者中MetS的存在是否会影响内质网（ER）、氧化应激以及白细胞-内皮细胞相互作用。
这是一项在学术医学中心进行的前瞻性对照研究。研究人群包括148例PCOS女性（116例无MetS/32例有MetS）和112例对照受试者（87例无MetS/25例有MetS）。测定了代谢参数、活性氧（ROS）生成、ER应激标志物（GRP78、sXBP1、ATF6）、白细胞-内皮细胞相互作用、黏附分子（VCAM-1、ICAM-1、E-选择素）、TNF-α和IL-6。
在存在MetS的情况下，总ROS、炎症参数和黏附分子增加（p<0.05），PCOS+MetS组的IL-6和ICAM-1水平高于对照组（p<0.05）。与各自的对照组相比，PCOS组和PCOS+MetS组观察到黏附增加和白细胞滚动通量增加（p<0.05）。GRP78蛋白表达在PCOS组中较高（与对照组相比，p<0.05），且sXBP1与MetS的存在相关（与无MetS的对照组相比，p<0.05）。此外，PCOS+MetS患者的GRP78和ATF6水平高于对照组和无MetS的PCOS患者（p<0.05）。在PCOS女性中，HOMA-IR与ICAM-1（r=0.501；p<0.01）、ROS（r=0.604；p<0.01）、滚动通量（r=0.455；p<0.05）和GRP78（r=0.574；p<0.001）呈正相关。
我们的研究结果支持以下假设，即PCOS患者代谢状态改变、ROS生成增加、ER应激和白细胞-内皮细胞相互作用之间存在关联，所有这些都与血管并发症有关。
