Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA.
Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA.
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DOI：
10.1038/s41467-018-03961-y
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发表时间：
2018-04-24
影响因子：
16.6
通讯作者：
Dor Y
中科院分区：
文献类型：
--
作者：
Zemmour H;Planer D;Magenheim J;Moss J;Neiman D;Gilon D;Korach A;Glaser B;Shemer R;Landesberg G;Dor Y
心肌细胞死亡的检测对于心脏病的诊断和治疗至关重要。在这里，我们使用比较甲基化组分析来鉴定心肌细胞中特异性未甲基化的基因组位点，并将其开发为生物标志物，以定量来自垂死细胞的循环无细胞DNA（cfDNA）中的心肌细胞DNA。健康个体的血浆基本上不含心肌细胞cfDNA，这与最小的心脏周转一致。急性ST段抬高心肌梗死患者显示出强有力的心脏cfDNA信号，该信号与肌钙蛋白和肌酸磷酸激酶（CPK）水平相关，包括冠状动脉血管成形术后预期的升高-衰减动力学。脓毒症患者具有强有力地预测死亡率的高心脏cfDNA浓度，表明心肌细胞死亡在脓毒症死亡率中的主要作用。心肌细胞死亡的cfDNA生物标志物可用于心脏病理学的诊断和监测以及正常人类心脏生理学和发育的研究。心肌细胞死亡的检测是心脏疾病诊断和监测的关键方面。在这里，作者表明，循环游离DNA的心肌细胞特异性甲基化模式可以作为梗死和脓毒症患者心脏细胞死亡的生物标志物。
Detection of cardiomyocyte death is crucial for the diagnosis and treatment of heart disease. Here we use comparative methylome analysis to identify genomic loci that are unmethylated specifically in cardiomyocytes, and develop these as biomarkers to quantify cardiomyocyte DNA in circulating cell-free DNA (cfDNA) derived from dying cells. Plasma of healthy individuals contains essentially no cardiomyocyte cfDNA, consistent with minimal cardiac turnover. Patients with acute ST-elevation myocardial infarction show a robust cardiac cfDNA signal that correlates with levels of troponin and creatine phosphokinase (CPK), including the expected elevation-decay dynamics following coronary angioplasty. Patients with sepsis have high cardiac cfDNA concentrations that strongly predict mortality, suggesting a major role of cardiomyocyte death in mortality from sepsis. A cfDNA biomarker for cardiomyocyte death may find utility in diagnosis and monitoring of cardiac pathologies and in the study of normal human cardiac physiology and development. The detection of cardiomyocyte death is a critical aspect in the diagnosis and monitoring of heart diseases. Here the authors show that cardiomyocyte-specific methylation patterns of circulating cell-free DNA may serve as a biomarker of cardiac cell death in infarcted and septic patients.
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影响因子：
17.1
作者：
De Vlaminck I;Valantine HA;Snyder TM;Strehl C;Cohen G;Luikart H;Neff NF;Okamoto J;Bernstein D;Weisshaar D;Quake SR;Khush KK
通讯作者：
Khush KK
影响因子：
158.5
作者：
Bianchi, Diana W.;Parker, R. Lamar;Sehnert, Amy J.
通讯作者：
Sehnert, Amy J.
严重败血症患者的预后效用和无细胞DNA的表征。
DOI：
10.1186/cc11466
发表时间：
2012-08-13
期刊：
Critical care (London, England)
影响因子：
--
作者：
Dwivedi DJ;Toltl LJ;Swystun LL;Pogue J;Liaw KL;Weitz JI;Cook DJ;Fox-Robichaud AE;Liaw PC;Canadian Critical Care Translational Biology Group
通讯作者：
Canadian Critical Care Translational Biology Group
影响因子：
2.8
作者：
Friden, Vincent;Starnberg, Karin;Hammarsten, Ola
通讯作者：
Hammarsten, Ola
影响因子：
--
作者：
Alcalai, Ronny;Planer, David;Lotan, Chaim
通讯作者：
Lotan, Chaim