Insulin resistance determines phagocytic nicotinamide adenine dinucleotide phosphate oxidase overactivation in metabolic syndrome patients
Insulin resistance determines phagocytic nicotinamide adenine dinucleotide phosphate oxidase overactivation in metabolic syndrome patients
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DOI：
10.1097/hjh.0b013e32832b1e8f
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发表时间：
2009-07-01
影响因子：
4.9
通讯作者：
Zalba, Guillermo
中科院分区：
文献类型：
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作者：
Fortuno, Ana;Bidegain, Julen;Zalba, Guillermo
目的 代谢综合征 (MetS) 与胰岛素抵抗相关，并增加心血管风险。氧化应激构成了将胰岛素抵抗和心血管疾病联系起来的潜在机制。本研究的目的是分析 NADPH 氧化酶激活与胰岛素抵抗的关系，以及这种相互作用对 MetS 患者心血管风险的影响。 方法 分别通过发光和蛋白质印迹法评估从 125 名 MetS 患者获得的外周血单核细胞中 NADPH 氧化酶依赖性超氧化物的产生和表达。胰岛素抵抗由稳态模型评估指数定义。通过酶联免疫吸附测定对血浆样品中的基质金属蛋白酶-9 进行定量。为了确定体内涉及的机制，我们在培养的巨噬细胞中进行了体外实验。结果 56% 的 MetS 患者表现出胰岛素抵抗。胰岛素抵抗患者的血浆基质金属蛋白酶-9 水平高于胰岛素敏感性患者（P < 0.05）。与胰岛素敏感患者相比，胰岛素抵抗患者的 NADPH 氧化酶依赖性超氧化物产生增加（P < 0.05）。胰岛素抵抗和 NADPH 氧化酶介导的超氧化物产生异常高之间的相互作用与最高基质金属蛋白酶 9 值相关。与胰岛素敏感患者相比，胰岛素抵抗患者 NADPH 氧化酶依赖性超氧化物产生的增加与较高的 NADPH 氧化酶 p22(phox) 表达显着相关。有趣的是，胰岛素上调外周血单核细胞和小鼠巨噬细胞中的p22(phox)。结论胰岛素抵抗与吞噬细胞NADPH氧化酶激活有关。这种关联导致 MetS 患者的心血管风险最高。 J Hypertens 27:1420-1430 (C) 2009 Wolters Kluwer Health |利平科特·威廉姆斯和威尔金斯。
Objective Metabolic syndrome (MetS) is associated with insulin resistance and increases the cardiovascular risk. Oxidative stress constitutes a potential mechanism that links insulin resistance and cardiovascular disease. The aim of this study was to analyze the relationship of NADPH oxidase activation with insulin resistance, and the effect of this interaction on the cardiovascular risk in MetS patients.Methods NADPH oxidase-dependent superoxide production and expression was evaluated by luminescence and western blot, respectively, in peripheral blood mononuclear cells obtained from 125 patients with MetS. Insulin resistance was defined by the homeostasis model assessment index. Matrix metalloproteinase-9 was quantified by enzyme-linked immunosorbent assay in plasma samples. To ascertain the mechanisms involved in vivo, we performed in-vitro experiments in cultured macrophages.Results Fifty- six percent of patients with MetS showed insulin resistance. Plasma matrix metalloproteinase-9 levels were higher (P < 0.05) in insulin-resistant patients than in patients with insulin sensitivity. NADPH oxidase-dependent superoxide production was augmented (P < 0.05) in insulin-resistant patients with respect to insulin-sensitive patients. The interaction between insulin resistance and abnormally high NADPH oxidase-mediated superoxide production was associated with the highest matrix metalloproteinase- 9 values. Increased NADPH oxidase-dependent superoxide production was significantly associated with higher NADPH oxidase p22(phox) expression in insulin-resistant than in insulin-sensitive patients. Interestingly, insulin upregulated p22(phox) in peripheral blood mononuclear cells and in murine macrophages.Conclusion Insulin resistance is associated with phagocytic NADPH oxidase activation. This association results in the highest cardiovascular risk in MetS patients. J Hypertens 27:1420-1430 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.