Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA

被引:152
作者
Zemmour, Hai [1 ]
Planer, David [2 ]
Magenheim, Judith [1 ]
Moss, Joshua [1 ]
Neiman, Daniel [1 ]
Gilon, Dan [2 ]
Korach, Amit [3 ]
Glaser, Benjamin [4 ]
Shemer, Ruth [1 ]
Landesberg, Giora [5 ]
Dor, Yuval [1 ]
机构
[1] Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel
[2] Hadassah Hebrew Univ, Med Ctr, Dept Cardiol, IL-91120 Jerusalem, Israel
[3] Hadassah Hebrew Univ, Med Ctr, Dept Cardiothorac Surg, IL-91120 Jerusalem, Israel
[4] Hadassah Hebrew Univ, Med Ctr, Endocrinol & Metab Serv, IL-91120 Jerusalem, Israel
[5] Hadassah Hebrew Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, IL-91120 Jerusalem, Israel
关键词
CARDIAC TROPONIN-T; DIASTOLIC DYSFUNCTION; SEVERE SEPSIS; CLEARANCE; DYNAMICS; IDENTIFICATION; MORTALITY; ELEVATION; RELEASE;
D O I
10.1038/s41467-018-03961-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:9
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