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Role of miRNA–mRNA Interactome in Pathophysiology of Arrhythmogenic Cardiomyopathy

Authors :
Fernando Bonet
Oscar Campuzano
José Córdoba-Caballero
Mireia Alcalde
Georgia Sarquella-Brugada
Aitana Braza-Boïls
Ramon Brugada
Francisco Hernández-Torres
Maribel Quezada-Feijoo
Monica Ramos
Alipio Mangas
Juan A. G. Ranea
Rocío Toro
Source :
Biomedicines, Vol 12, Iss 8, p 1807 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Arrhythmogenic cardiomyopathy is an inherited entity characterized by irregular cell–cell adhesion, cardiomyocyte death and fibro-fatty replacement of ventricular myocytes, leading to malignant ventricular arrythmias, contractile dysfunction and sudden cardiac death. Pathogenic variants in genes that encode desmosome are the predominant cause of arrhythmogenic cardiomyopathy. Moreover, signalling pathways such as Wnt/ß-catenin and transforming growth factor-β have been involved in the disease progression. However, still little is known about the molecular pathophysiological mechanisms that underlie arrhythmogenic cardiomyopathy pathogenesis. We used mRNA and small RNA sequencing to analyse the transcriptome of health and arrhythmogenic cardiomyopathy of autopsied human hearts. Our results showed 697 differentially expressed genes and eight differentially expressed miRNAs. Functional enrichment revealed mitochondrial respiratory-related pathways, impaired response to oxidative stress, apoptotic signalling pathways and inflammatory response-related and extracellular matrix response pathways. Furthermore, analysis of the miRNA–mRNA interactome identified eleven negatively correlated miRNA-target pairs for arrhythmogenic cardiomyopathy. Our finding revealed novel arrhythmogenic cardiomyopathy-related miRNAs with important regulatory function in disease pathogenesis, highlighting their value as potential key targets for therapeutic approaches.

Details

Language :
English
ISSN :
22279059
Volume :
12
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
edsdoj.945d2dc181984d7480a2a40bb22752e5
Document Type :
article
Full Text :
https://doi.org/10.3390/biomedicines12081807