Abstract:
Cardiovascular disease (CVD) is a leading global cause of mortality, difficult to predict in advance. Evidence indicates that the copy number of mitochondrial DNA (mtDNAcn) in blood is altered in individuals with CVD. MtDNA released into circulation may act as a mediator of inflammation, a recognized factor in the development of CVD, in the long distance. This pilot study aims to test if levels of mtDNAcn in buffy coat DNA (BC-mtDNA), in circulating cellfree DNA (cf-mtDNA), or in DNA extracted from plasma extracellular vesicles (EV-mtDNA) are altered in CVD patients and if they can predict heart attack in advance. A group of 144 people with different CVD statuses (50 that had CVD, 94 healthy) was selected from the LifeLines Biobank according to the incidence of new cardiovascular event monitored in 6 years (50 among controls had heart attack after the basal assessment). MtDNAcn was quantified in total cf-DNA and EV-DNA from plasma as well as in buffy coat. EVs have been characterized by their size, polydispersity index, count rate, and zeta potential, by Dynamic Light Scattering. BC-mtDNAcn and cf-mtDNAcn were not different between CVD patients and healthy subjects. EVs carried higher mtDNAcn in subject with a previous history of CVD than controls, also adjusting the analysis for the EVs derived count rate. Despite mtDNAcn was not able to predict CVD in advance, the detection of increased EV-mtDNAcn in CVD patients in this pilot study suggests the need for further investigations to determine its pathophysiological role in inflammation.
摘要:
心血管疾病(CVD)是全球主要的死亡原因,很难提前预测。证据表明,血液中线粒体DNA(mtDNAcn)的拷贝数在患有CVD的个体中发生了改变。释放到循环中的MtDNA可能是炎症的介质,CVD发展的一个公认因素,在遥远的距离。这项初步研究旨在测试血沉棕黄层DNA(BC-mtDNA)中mtDNAcn的水平,在循环无细胞DNA(cf-mtDNA)中,或从血浆细胞外囊泡(EV-mtDNA)中提取的DNA在CVD患者中改变,如果他们可以提前预测心脏病发作。一组144人具有不同的CVD状态(50人患有CVD,根据6年内监测的新心血管事件发生率,从LifeLines生物库中选择94名健康者)(在基础评估后,对照组中有50名心脏病发作)。在来自血浆以及血沉棕黄层中的总cf-DNA和EV-DNA中定量MtDNAcn。电动汽车的特点是它们的大小,多分散指数,计数率,和zeta电位,通过动态光散射。BC-mtDNAcn和cf-mtDNAcn在CVD患者和健康受试者之间没有差异。在有心血管疾病病史的受试者中,电动汽车携带的mtDNAcn高于对照组,还调整了对电动汽车得出的计数率的分析。尽管mtDNAcn无法提前预测CVD,在这项初步研究中,在CVD患者中检测到EV-mtDNAcn升高,提示需要进一步研究以确定其在炎症中的病理生理作用.