Circulating cell-free DNA fragment analysis by microchip electrophoresis and its relationship with DNase I in cardiac diseases
Circulating cell-free DNA fragment analysis by microchip electrophoresis and its relationship with DNase I in cardiac diseases
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DOI：
10.1016/j.cca.2019.07.014
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发表时间：
2019-10-01
影响因子：
5
通讯作者：
Takeshita, Haruo
中科院分区：
文献类型：
--
作者：
Fujihara, Junko;Takinami, Yoshikazu;Takeshita, Haruo
循环游离DNA（cfDNA）与癌症、糖尿病、中风、系统性红斑狼疮、创伤、类风湿性关节炎、炎症、感染以及心肌梗死（MI）直接相关。在本研究中，从心脏病患者的血浆中提取血浆cfDNA，并检测cfDNA片段分布以及cfDNA浓度与参与双链DNA加工的脱氧核糖核酸酶I（DNase I）活性酶之间的关系。结果显示，心肌梗死和心绞痛患者的cfDNA浓度显著高于健康对照组。血浆cfDNA的微芯片电泳显示，一些健康对照组中存在单个片段（150 - 200 bp），而所有心脏病患者样本中存在三个片段（150 - 200 bp、300 - 400 bp和500 - 600 bp）。此外，150 - 200 bp/500 - 600 bp的cfDNA比值在心肌梗死患者中比在其他心脏病（胸痛、心绞痛、心房颤动和心力衰竭）患者中更为普遍。此外，还观察到DNase I活性与cfDNA浓度之间呈正相关。这些结果表明，心脏病患者的血浆cfDNA可能来源于细胞凋亡，并且cfDNA的150 - 200 bp/500 - 600 bp比值可能是心肌梗死的一种新型诊断指标。
Circulating cell-free DNA (cfDNA) has been directly related to cancer, diabetes, stroke, systemic lupus erythematosus, trauma, rheumatoid arthritis, inflammation, infection, and myocardial infarction (MI). In this study, plasma cfDNA was extracted from the plasma of cardiac disease patients and the cfDNA fragment distribution as well as the relationships between cfDNA concentration and deoxyribonuclease I (DNase I) activity enzyme implicated in double-stranded DNA processing were examined. Results revealed that the cfDNA concentrations in patients with MI and cardiac angina were significantly higher than that in healthy control subjects. Microchip electrophoresis of plasma cfDNA revealed a single fragment (150-200 bp) in some healthy control subjects and three fragments (150-200 bp, 300-400 bp, and 500-600 bp) in all cardiac patient samples. Moreover, a cfDNA ratio of 150-200 bp/500-600 bp was significantly more prevalent in MI patients than in patients with other cardiac diseases (chest pain, cardiac angina, atrial fibrillation and cardiac failure). In addition, a positive correlation between DNase I activity and cfDNA concentration was observed. These results suggest that the plasma cfDNA in cardiac disease patients may originate from apoptosis and that the 150-200 bp/500-600 bp ratio for cfDNA may be a novel diagnostic indicator for MI.