Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA.
Hai ZemmourDavid PlanerJudith MagenheimJoshua MossDaniel NeimanDan GilonAmit KorachBenjamin GlaserRuth ShemerGiora LandesbergYuval DorPublished in: Nature communications (2018)
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.
Keyphrases
- angiotensin ii
- left ventricular
- endothelial cells
- high glucose
- st elevation myocardial infarction
- coronary artery disease
- acute kidney injury
- circulating tumor
- intensive care unit
- cardiovascular events
- percutaneous coronary intervention
- dna methylation
- induced apoptosis
- coronary artery
- single molecule
- induced pluripotent stem cells
- palliative care
- genome wide
- type diabetes
- gene expression
- cell proliferation
- septic shock
- pluripotent stem cells
- transcatheter aortic valve replacement
- cell death
- oxidative stress
- acute coronary syndrome
- bone mineral density
- signaling pathway
- endoplasmic reticulum stress
- aortic stenosis
- real time pcr
- ejection fraction