Induction of Oxidative Stress and Human Leukocyte/Endothelial Cell Interactions in Polycystic Ovary Syndrome Patients with Insulin Resistance
Induction of Oxidative Stress and Human Leukocyte/Endothelial Cell Interactions in Polycystic Ovary Syndrome Patients with Insulin Resistance
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DOI：
10.1210/jc.2011-0651
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发表时间：
2011-10-01
影响因子：
5.8
通讯作者：
Hernandez-Mijares, Antonio
中科院分区：
文献类型：
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作者：
Victor, Victor M.;Rocha, Milagros;Hernandez-Mijares, Antonio
内容：胰岛素抵抗是多囊卵巢综合征（PCOS）的一个特征，与线粒体和内皮功能有关。目的：我们检测高雄激素胰岛素抵抗的PCOS妇女是否具有血管疾病的风险增加，显示白细胞-内皮相互作用受损和线粒体功能障碍。设计和设置：这是一项在学术医学中心进行的前瞻性对照研究。患者：研究人群包括43瘦育龄妇女PCOS和39对照subjects.Main结果Measures：我们评估人体测量和代谢参数，粘附分子，白细胞和人脐静脉内皮细胞之间的相互作用。通过评估多形核细胞中线粒体耗氧量、膜电位、活性氧产生、谷胱甘肽水平（GSH）和氧化型谷胱甘肽（GSSG）/GSH比率来研究线粒体功能。在PCOS患者中观察到线粒体功能受损，明显表现为耗氧量减少，活性氧产生增加，GSH/GSSG比值和GSH水平的降低，以及膜电位的破坏。多囊卵巢综合征与多形核细胞滚动速度下降、滚动流量和粘附力增加有关。IL-6和TNF α和粘附分子（血管细胞粘附分子-1和E-选择素）的增加也observed.Conclusion：这项研究支持胰岛素抵抗和受损的内皮细胞和线粒体氧化代谢之间的关联的假设。所获得的证据表明，PCOS中与胰岛素抵抗相关的炎症状态诱导白细胞-内皮细胞相互作用。这些发现可以解释PCOS女性血管疾病风险增加的原因。（临床内分泌代谢杂志96：3115-3122，2011）
Context: Insulin resistance is a feature of polycystic ovary syndrome (PCOS) and is related to mitochondrial and endothelial function.Objective: We tested whether hyperandrogenic insulin-resistant women with PCOS, who have an increased risk of vascular disease, display impaired leukocyte-endothelium interactions, and mitochondrial dysfunction.Design and Setting: This was a prospective controlled study conducted in an academic medical center.Patients: The study population consisted of 43 lean reproductive-age women with PCOS and 39 controls subjects.Main Outcome Measures: We evaluated anthropometric and metabolic parameters, adhesion molecules, and interactions between leukocytes and human umbilical vein endothelial cells. Mitochondrial function was studied by assessing mitochondrial oxygen consumption, membrane potential, reactive oxygen species production, glutathione levels (GSH), and the oxidized glutathione (GSSG)/GSH ratio in polymorphonuclear cells.Results: Impairment of mitochondrial function was observed in the PCOS patients, evident in a decrease in oxygen consumption, an increase in reactive oxygen species production, a decrease in the GSH/GSSG ratio and GSH levels, and an undermining of the membrane potential. PCOS was related to a decrease in polymorphonuclear cell rolling velocity and an increase in rolling flux and adhesion. Increases in IL-6 and TNF alpha and adhesion molecules (vascular cell adhesion molecule-1 and E-selectin) were also observed.Conclusion: This study supports the hypothesis of an association between insulin resistance and an impaired endothelial and mitochondrial oxidative metabolism. The evidence obtained shows that the inflammatory state related to insulin resistance in PCOS induces a leukocyte-endothelium interaction. These findings may explain the increased risk of vascular disease in women with PCOS. (J Clin Endocrinol Metab 96: 3115-3122, 2011)