Tolstik Taisiya V, Kirichenko Tatiana V, Markin Alexander M, Bogatyreva Anastasia I, Markina Yuliya V, Kiseleva Diana G, Shaposhnikova Nataliya N, Starodubova Antonina V, Orekhov Alexander N
Petrovsky National Research Center of Surgery, Moscow, Russia.
Chazov National Medical Research Center of Cardiology, Moscow, Russia.
Front Mol Biosci. 2024 Mar 20;11:1362955. doi: 10.3389/fmolb.2024.1362955. eCollection 2024.
Mitochondrial dysfunction may be one of the causes of inflammatory activation of monocytes and macrophages, which leads to excessive secretion of inflammatory mediators and the development of chronic inflammation.
The study was aimed to evaluate the secretion of inflammatory cytokine tumor necrosis factor-α (TNF-α) in the primary culture of monocytes, and to analyze its relationship with the number of mitochondrial DNA (mtDNA) copies in the blood of patients with coronary heart disease (CHD) and obesity.
108 patients with obesity and concomitant CHD and a control group of 25 participants were included in the study. CD14 monocytes were isolated by a standard method in a ficoll-urographin gradient, followed by separation using magnetic particles. The number of mtDNA copies was estimated using qPCR.
It was demonstrated that the number of mtDNA copies was significantly increased in groups of patients with CHD and obesity + CHD in comparison with control group. mtDNA copy number positively correlated with basal and LPS-stimulated TNF-α secretion, the most significant correlation was found in the group of patients with CHD and obesity.
Thus, the change in mtDNA copy number in CD14 monocytes which indicates the presence of mitochondrial dysfunction, confirm the direct involvement of mitochondria in the violation of the inflammatory response of monocytes revealed in this study as an increased secretion of inflammatory cytokine TNF-α.
线粒体功能障碍可能是单核细胞和巨噬细胞炎症激活的原因之一,这会导致炎症介质过度分泌以及慢性炎症的发展。
本研究旨在评估单核细胞原代培养中炎性细胞因子肿瘤坏死因子-α(TNF-α)的分泌情况,并分析其与冠心病(CHD)和肥胖患者血液中线粒体DNA(mtDNA)拷贝数的关系。
本研究纳入了108例肥胖合并冠心病患者以及25名参与者作为对照组。通过在菲可-泛影葡胺梯度中采用标准方法分离CD14单核细胞,随后使用磁性颗粒进行分离。使用qPCR估算mtDNA拷贝数。
结果表明,与对照组相比,冠心病组和肥胖合并冠心病组患者的mtDNA拷贝数显著增加。mtDNA拷贝数与基础和脂多糖刺激的TNF-α分泌呈正相关,在冠心病和肥胖患者组中发现的相关性最为显著。
因此,CD14单核细胞中mtDNA拷贝数的变化表明存在线粒体功能障碍,证实了线粒体直接参与了本研究中揭示的单核细胞炎症反应异常,即炎性细胞因子TNF-α分泌增加。