Knez Judita, Marrachelli Vannina G, Cauwenberghs Nicholas, Winckelmans Ellen, Zhang Zhenyu, Thijs Lutgarde, Brguljan-Hitij Jana, Plusquin Michelle, Delles Christian, Monleon Daniel, Redón Josep, Staessen Jan A, Nawrot Tim S, Kuznetsova Tatiana
Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Department of Hypertension, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia.
PLoS One. 2017 Jul 13;12(7):e0181036. doi: 10.1371/journal.pone.0181036. eCollection 2017.
Mitochondrial DNA (mtDNA) content might undergo significant changes caused by metabolic derangements, oxidative stress and inflammation that lead to development and progression of cardiovascular diseases. We, therefore, investigated in a general population the association of peripheral blood mtDNA content with circulating metabolites and inflammatory markers. We examined 310 subjects (50.6% women; mean age, 53.3 years) randomly selected from a Flemish population. Relative mtDNA content was measured by quantitative real-time PCR in peripheral blood cells. Peak circulating metabolites were quantified using nuclear magnetic resonance spectroscopy. The level of inflammation was assessed via established inflammatory markers. Using Partial Least Squares analysis, we constructed 3 latent factors from the 44 measured metabolites that explained 62.5% and 8.5% of the variance in the contributing metabolites and the mtDNA content, respectively. With adjustments applied, mtDNA content was positively associated with the first latent factor (P = 0.002). We identified 6 metabolites with a major impact on the construction of this latent factor including HDL3 apolipoproteins, tyrosine, fatty acid with αCH2, creatinine, β-glucose and valine. We summarized them into a single composite metabolite score. We observed a negative association between the composite metabolic score and mtDNA content (P = 0.001). We also found that mtDNA content was inversely associated with inflammatory markers including hs-CRP, hs-IL6, white blood cell and neutrophil counts as well as neutrophil-to-lymphocyte ratio (P≤0.0024). We demonstrated that in a general population relative peripheral blood mtDNA content was associated with circulating metabolites indicative of perturbed lipid metabolism and with inflammatory biomarkers.
线粒体DNA（mtDNA）含量可能会因代谢紊乱、氧化应激和炎症而发生显著变化，这些变化会导致心血管疾病的发生和发展。因此，我们在普通人群中研究了外周血mtDNA含量与循环代谢物及炎症标志物之间的关联。我们检查了从佛兰德人群中随机选取的310名受试者（50.6%为女性；平均年龄53.3岁）。通过定量实时PCR测量外周血细胞中的相对mtDNA含量。使用核磁共振波谱法定量循环代谢物峰值。通过既定的炎症标志物评估炎症水平。使用偏最小二乘法分析，我们从44种测量的代谢物中构建了3个潜在因子，它们分别解释了贡献代谢物和mtDNA含量中62.5%和8.5%的方差。经过调整后，mtDNA含量与第一个潜在因子呈正相关（P = 0.002）。我们确定了对该潜在因子构建有重大影响的6种代谢物，包括高密度脂蛋白3载脂蛋白、酪氨酸、含αCH2的脂肪酸、肌酐、β-葡萄糖和缬氨酸。我们将它们汇总为一个单一的复合代谢物评分。我们观察到复合代谢评分与mtDNA含量之间呈负相关（P = 0.001）。我们还发现，mtDNA含量与包括高敏C反应蛋白、高敏白细胞介素6、白细胞和中性粒细胞计数以及中性粒细胞与淋巴细胞比值在内的炎症标志物呈负相关（P≤0.0024）。我们证明，在普通人群中，外周血相对mtDNA含量与指示脂质代谢紊乱的循环代谢物以及炎症生物标志物相关。
