Methylome-driven regulation of miRNA expression and its relationship to cardiac dysfunction in idiopathic dilated cardiomyopathy.

Autores de IIS La Fe

• Alex Gallego Martinez

  Autor

• Marta Delgado Arija

  Autor

• Irene González Torrent

  Autor

• Lorena Pérez Carrillo

  Autor

• Carlota Benedicto Marrero

  Autor

• Joan Bodi Miret

  Autor

• Manuel Portoles Sanz

  Autor

• Estefanía Tarazón Melguizo

  Autor

• 

  Esther Roselló Lletí

  Autor

Grupos

• Grupo de Investigación Clínica y Traslacional en Cardiología

Abstract

BACKGROUND: Idiopathic dilated cardiomyopathy (iDCM) is a multifactorial disease with a complex pathogenesis involving diverse molecular mechanisms. Among these, epigenetic mechanisms, including both DNA methylation and microRNAs (miRNAs)-mediated regulation, play an important role in determining the disease phenotype. However, the interplay between the DNA methylome and the miRNA transcriptome in iDCM remains largely unexplored. METHODS: We conducted a cross-cohort multiomic integrative analysis of left ventricular (LV) tissue samples from iDCM patients and control (CNT) donors. DNA methylation profiling was performed using the Infinium MethylationEPIC BeadChip, whereas ncRNA-seq was used to assess transcriptomic changes. RESULTS: We identified a subset of three miRNAs exhibiting both differential methylation in their promoter regions and differential expression in their primary and mature forms. Notably, the miRNA hsa-miR-433-3p (r = 0.671, p < 0.01), which is involved in fibrotic pathways, appear to be significantly correlated with the left ventricular ejection fraction (LVEF), an established echocardiographic marker of cardiac function. CONCLUSIONS: This study enhances our understanding of the epigenetic mechanisms shaping the miRNA transcriptomic landscape in iDCM, suggesting potential roles for these miRNAs in cardiac dysfunction and myocardial fibrosis.

© 2025. The Author(s).

Keywords

• DNA methylation; Epigenomics; Idiopathic dilated cardiomyopathy; MicroRNAs