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Distinguishable DNA methylation defines a cardiac-specific epigenetic clock

  • Mongelli, A.
  • Panunzi, S.
  • Nesta, M.
  • Gottardi Zamperla, M.
  • Atlante, S.
  • Barbi, V.
  • Mongiardini, V.
  • Ferraro, F.
  • De Martino, S.
  • Cis, L.
  • Re, A.
  • Maltese, S.
  • Bachetti, T.
  • La Rovere, M. T.
  • Martelli, F.
  • Pesce, M.
  • Nanni, S.
  • Massetti, M.
  • Pontecorvi, A.
  • Farsetti, A.
  • And 1 more
Published Article
Clinical Epigenetics
Publication Date
Mar 29, 2023
DOI: 10.1186/s13148-023-01467-z
PMID: 36991505
PMCID: PMC10053964
PubMed Central
  • Research


Background The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age. Results Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume. Conclusion This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-023-01467-z.

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