Indirect epigenetic testing identifies a diagnostic signature of cardiomyocyte DNA methylation in heart failure

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Christian U. Oeing - , Universität Heidelberg, Charité – Universitätsmedizin Berlin (Autor:in)
  • Mark E. Pepin - , Universität Heidelberg (Autor:in)
  • Kerstin B. Saul - , Universität Heidelberg (Autor:in)
  • Ayça Seyhan Agircan - , Universität Heidelberg (Autor:in)
  • Yassen Assenov - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Tobias S. Merkel - , Universität Heidelberg (Autor:in)
  • Farbod Sedaghat-Hamedani - , Universität Heidelberg (Autor:in)
  • Tanja Weis - , Universität Heidelberg (Autor:in)
  • Benjamin Meder - , Universität Heidelberg (Autor:in)
  • Kaomei Guan - , Institut für Pharmakologie und Toxikologie, Technische Universität Dresden (Autor:in)
  • Christoph Plass - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Dieter Weichenhan - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Dominik Siede - , Universität Heidelberg (Autor:in)
  • Johannes Backs - , Universität Heidelberg (Autor:in)


Precision-based molecular phenotyping of heart failure must overcome limited access to cardiac tissue. Although epigenetic alterations have been found to underlie pathological cardiac gene dysregulation, the clinical utility of myocardial epigenomics remains narrow owing to limited clinical access to tissue. Therefore, the current study determined whether patient plasma confers indirect phenotypic, transcriptional, and/or epigenetic alterations to ex vivo cardiomyocytes to mirror the failing human myocardium. Neonatal rat ventricular myocytes (NRVMs) and single-origin human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and were treated with blood plasma samples from patients with dilated cardiomyopathy (DCM) and donor subjects lacking history of cardiovascular disease. Following plasma treatments, NRVMs and hiPSC-CMs underwent significant hypertrophy relative to non-failing controls, as determined via automated high-content screening. Array-based DNA methylation analysis of plasma-treated hiPSC-CMs and cardiac biopsies uncovered robust, and conserved, alterations in cardiac DNA methylation, from which 100 sites were validated using an independent cohort. Among the CpG sites identified, hypo-methylation of the ATG promoter was identified as a diagnostic marker of HF, wherein cg03800765 methylation (AUC = 0.986, P < 0.0001) was found to out-perform circulating NT-proBNP levels in differentiating heart failure. Taken together, these findings support a novel approach of indirect epigenetic testing in human HF.


FachzeitschriftBasic research in cardiology
PublikationsstatusVeröffentlicht - Dez. 2023

Externe IDs

PubMed 36939901


Ziele für nachhaltige Entwicklung


  • DNA methylation, Epigenetics, Heart failure, Pilot study, Precision medicine, Epigenomics, Myocytes, Cardiac/pathology, Humans, Epigenesis, Genetic, Rats, DNA Methylation, Heart Failure/diagnosis, Animals, Induced Pluripotent Stem Cells