Human Leukocyte/Endothelial Cell Interactions and Mitochondrial Dysfunction in Type 2 Diabetic Patients and Their Association With Silent Myocardial Ischemia
Human Leukocyte/Endothelial Cell Interactions and Mitochondrial Dysfunction in Type 2 Diabetic Patients and Their Association With Silent Myocardial Ischemia
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DOI：
10.2337/dc12-1224
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发表时间：
2013-06-01
期刊：
影响因子：
16.2
通讯作者：
Victor, Victor M.
中科院分区：
文献类型：
--
作者：
Hernandez-Mijares, Antonio;Rocha, Milagros;Victor, Victor M.
糖尿病与氧化应激和死亡率增加有关，但白细胞-内皮细胞相互作用，氧化应激，研究设计和方法-在200例2型糖尿病患者中评估线粒体功能障碍和白细胞与人脐静脉内皮细胞之间的相互作用（25例SMI）和60名身体成分和年龄匹配的对照组受试者。探讨了这些参数与SMI发作之间的可能相关性，并分析了人体测量和代谢参数。（白细胞介素-6和肿瘤坏死因子-α、HbA（1c）、高敏C反应蛋白（hs-CRP）、葡萄糖和胰岛素，胰岛素抵抗和稳态模型评估在糖尿病患者中高于对照组。然而，当数据校正腰围时，未检测到hs-CRP和胰岛素水平的统计学差异。这些参数在SMI和非SMI患者之间均无变化。在糖尿病患者中线粒体功能受损并且白细胞-内皮相互作用更频繁，这在较低的线粒体O2消耗、膜电位、多形核细胞滚动速度和GSH/GSSG比率中以及在这些受试者中观察到的较高的线粒体活性氧产生和滚动通量、粘附和血管细胞粘附分子-1（VCAM-1）和E-选择素分子中是明显的。此外，这些差异与SMI相关。调整BMI和腰围的数据后，保持统计学差异，VCAM-1水平调整时，腰围。结论氧化应激，线粒体功能障碍，内皮诱导的白细胞-内皮细胞相互作用的2型糖尿病的特点，并与SMI相关。
OBJECTIVE-Diabetes is associated with oxidative stress and increased mortality, but a possible correlation between leukocyte-endothelium interactions, oxidative stress, and silent myocardial ischemia (SMI) is yet to be confirmed.RESEARCH DESIGN AND METHODS-Mitochondrial dysfunction and interactions between leukocytes and human umbilical vein endothelial cells were evaluated in 200 type 2 diabetic patients (25 with SMI) and 60 body composition and age-matched control subjects. A possible correlation between these parameters and the onset of SMI was explored, and anthropometric and metabolic parameters were also analyzed.RESULTS-Waist, levels of triglycerides, proinflammatory cytokines (interleukin-6 and tumor necrosis factor-alpha, HbA(1c), high-sensitivity C-reactive protein (hs-CRP), glucose, and insulin, and homeostasis model assessment of insulin resistance were higher in diabetic patients than in control subjects. However, no statistical differences in hs-CRP and insulin levels were detected when the data were adjusted for waist. None of these parameters varied between SMI and non-SMI patients. Mitochondrial function was impaired and leukocyte-endothelium interactions were more frequent among diabetic patients, which was evident in the lower mitochondrial 02 consumption, membrane potential, polymorphonuclear cell rolling velocity, and GSH/GSSG ratio, and in the higher mitochondrial reactive oxygen species production and rolling flux, adhesion, and vascular cell adhesion molecule-1 (VCAM-1) and E-selectin molecules observed in these subjects. Moreover, these differences correlated with SMI. Statistical differences were maintained after adjusting the data for BMI and waist, with the exception of VCAM-1 levels when adjusted for waist.CONCLUSIONS-Oxidative stress, mitochondrial dysfunction, and endothelium-inducing leukocyte-endothelium interactions are features of type 2 diabetes and correlate with SMI.