Transcriptome analysis of miRNA and mRNA in the myocardial tissue of mice with LMNA-dilated cardiomyopathy

  1. Bonet, F.
  2. Villa, E. Alonso
  3. De Castro Insua, I. Perez
  4. Marti, B. Vilaplana
  5. Caballero, J. Cordoba
  6. Ranea, J.A.
  7. Hernandez-Torres, F.
  8. Quezada-Feijoo, M.
  9. Ramos, M.
  10. Perez-Perez, C.
  11. Campanario, I.
  12. Mangas, A.
  13. Toro, R.

ISSN: 0021-9150

Any de publicació: 2023

Volum: 379

Pàgines: S179-S180

Tipus: Article

DOI: 10.1016/J.ATHEROSCLEROSIS.2023.06.602 GOOGLE SCHOLAR lock_openAccés obert editor

Altres publicacions en: Atherosclerosis

Objetivos de desarrollo sostenible


Background and Aims: Lamin A/C (LMNA) gene mutations are a known cause of familial dilated cardiomyopathy (DCM). DCM linked to LMNA gene mutation (LMNA-DCM) is a highly penetrant and arrhythmogenic cardiomyopathy that leads to transplantation and premature sudden cardiac death. The precise mechanisms triggering disease progression remain unknown. In the current study, we investigated the mRNA and miRNA transcriptome in the myocardial tissue of 50-week-old wild-type and LMNAR249W mice to gain insights into the molecular pathogenesis of LMNA-DCM.Methods: We analyzed the mRNA and miRNA trascriptome by next-generation sequencing in cardiac tissue from six 50-week-old wild type mice with normal cardiac function and six LMNAR249W mice with DCM. Functional enrichment analysis of differentially expressed genes (DEGs) were performed using over representation analysis (ORA) for Gene Ontology, KEGG and Reactome. We analyzed miRNA-mRNA interactions to find miRNA-target regulation pairs (mTPs). The functions of miRNA target genes, previously validated in other studies, were also analyzed using ORA. All expression data analysis was performed using the ExpHunter suite.Results: 2148 genes (1485 upregulated and 663 downregulated) and 53 miRNAs (21 upregulated and 32 downregulated) were diferentially expressed in LMNAR249W hearts. Funtional enrichment analysis identified extracellular matrix regulation, fatty acid metabolism and calcium signaling among the most enrichment pathways. We found 1800 validated mTPs and the most significant functions of the targets are related to extracellular matrix, actinin and cytoeskeleton organization, and regulation of inflamatory response.Conclusions: These results revealed novel miRNA-mRNA interaction networks and signaling pathways for LMNA-DCM, providing novel insights into the development of this disease.