Relation of mitochondrial oxygen consumption in peripheral blood mononuclear cells to vascular function in type 2 diabetes mellitus
Relation of mitochondrial oxygen consumption in peripheral blood mononuclear cells to vascular function in type 2 diabetes mellitus
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DOI：
10.1177/1358863x14521315
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发表时间：
2014-02-01
影响因子：
3.5
通讯作者：
Vita, Joseph A.
中科院分区：
文献类型：
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作者：
Hartman, Mor-Li;Shirihai, Orian S.;Vita, Joseph A.
最近的研究表明，糖尿病患者外周血单个核细胞（PBMC）和内皮细胞中线粒体功能障碍和活性氧的产生增加。线粒体氧消耗与三磷酸腺苷（ATP）的产生偶联，并且在通过电子传递链和其他酶位点的组分形成活性氧物质期间也以非偶联方式发生。因此，我们假设糖尿病与PBMC中较高的总耗氧量和非偶联耗氧量相关，这与内皮功能障碍相关。我们开发了一种方法来测量新鲜分离的PBMC的耗氧量，并将其应用于26例2型糖尿病患者和28例非糖尿病对照。与对照组相比，糖尿病患者的基础（192 +/- 47 vs 161 +/- 44 pmol/min，p=0.01）、非偶联（64 +/- 16 vs 53 +/- 13 pmol/min，p=0.007）和最大（795 +/- 87 vs 715 +/- 128 pmol/min，p=0.01）耗氧率较高。耗氧率与血管超声测量的内皮依赖性血流介导的舒张功能之间无显著相关性。糖尿病患者的非内皮依赖性硝酸甘油介导的血管扩张较低（10.1 +/- 6.6 vs 15.8 +/-4.8%，p=0.03），并与最大耗氧量相关（r =-0.64，p=0.001）。总之，我们发现糖尿病与线粒体氧消耗模式相关，该模式与较高的活性氧产生一致。氧气消耗与硝酸甘油介导的扩张之间的相关性可能表明线粒体功能障碍与血管平滑肌细胞功能障碍之间存在联系，值得进一步研究。最后，所描述的方法可用于在人类中进行更大规模的观察性和干预性研究中评估线粒体功能。
Recent studies have shown mitochondrial dysfunction and increased production of reactive oxygen species in peripheral blood mononuclear cells (PBMCs) and endothelial cells from patients with diabetes mellitus. Mitochondria oxygen consumption is coupled to adenosine triphosphate (ATP) production and also occurs in an uncoupled fashion during formation of reactive oxygen species by components of the electron transport chain and other enzymatic sites. We therefore hypothesized that diabetes would be associated with higher total and uncoupled oxygen consumption in PBMCs that would correlate with endothelial dysfunction. We developed a method to measure oxygen consumption in freshly isolated PBMCs and applied it to 26 patients with type 2 diabetes mellitus and 28 non-diabetic controls. Basal (192 +/- 47 vs 161 +/- 44 pmoles/min, p=0.01), uncoupled (64 +/- 16 vs 53 +/- 13 pmoles/min, p=0.007), and maximal (795 +/- 87 vs 715 +/- 128 pmoles/min, p=0.01) oxygen consumption rates were higher in diabetic patients compared to controls. There were no significant correlations between oxygen consumption rates and endothelium-dependent flow-mediated dilation measured by vascular ultrasound. Non-endothelium-dependent nitroglycerin-mediated dilation was lower in diabetics (10.1 +/- 6.6 vs 15.8 +/- 4.8%, p=0.03) and correlated with maximal oxygen consumption (r =-0.64, p=0.001). In summary, we found that diabetes mellitus is associated with a pattern of mitochondrial oxygen consumption consistent with higher production of reactive oxygen species. The correlation between oxygen consumption and nitroglycerin-mediated dilation may suggest a link between mitochondrial dysfunction and vascular smooth muscle cell dysfunction that merits further study. Finally, the described method may have utility for the assessment of mitochondrial function in larger scale observational and interventional studies in humans.