Role of miRNA–mRNA Interactome in Pathophysiology of Arrhythmogenic Cardiomyopathy
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.
Authors
- Francisco Hernández‐Torres (ORCID: https://orcid.org/0000-0003-1343-8274)
- Georgia Sarquella‐Brugada (ORCID: https://orcid.org/0000-0002-6857-8904)
- Maribel Quezada-Feijoó (ORCID: https://orcid.org/0000-0002-9707-9899)
- Mónica Ramos (ORCID: https://orcid.org/0000-0002-8903-5343)
- Ramón Brugada
- Rocío Toro (ORCID: https://orcid.org/0000-0003-3136-1776)
- Aitana Braza‐Boïls (ORCID: https://orcid.org/0000-0002-9888-6705)
- Alipio Mangas (ORCID: https://orcid.org/0000-0002-5402-6674)
- Óscar Campuzano (ORCID: https://orcid.org/0000-0001-5298-5276)
- Fernando Bonet (ORCID: https://orcid.org/0000-0001-9855-8173)
- Juan A. G. Ranea (ORCID: https://orcid.org/0000-0003-0327-1837)
- J. Caballero (ORCID: https://orcid.org/0000-0002-1821-5742)
- Mireia Alcalde (ORCID: https://orcid.org/0000-0002-7222-0913)
Institutions
- Hospital Sant Joan de Déu Barcelona (ES)
- Universidad de Granada (ES)
- Universitat de Girona (ES)
- Instituto de Salud Carlos III (ES)
- Universidad de Cádiz (ES)
- Centro de Investigación en Red en Enfermedades Cardiovasculares (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Institut d'Investigació Biomèdica de Girona (ES)
- Hospital Central de la Cruz Roja San José y Santa Adela (ES)
- Biomedical Research and Innovation Institute of Cadiz (ES)
- Fundación Medina (ES)
- Hospital Universitario Puerta del Mar (ES)
- Universidad Alfonso X el Sabio (ES)
- Hospital Universitari de Girona Doctor Josep Trueta (ES)
- Instituto de Investigación Biomédica de Málaga (ES)
- Instituto de Investigación Sanitaria La Fe (ES)
- Institut de Recerca Sant Joan de Déu
- Universidad de Málaga (ES)
Publication Details
- Journal
- Biomedicines
- Published
- 2024-08-09
- DOI
- https://doi.org/10.3390/biomedicines12081807
- Citations
- 3
- Primary Topic
- Cardiovascular Effects of Exercise
- Type
- article
- Field-Weighted Citation Impact
- 1.21
Funders
- Sociedad Española de Cardiología
- Centres de Recerca de Catalunya
- European Commission
- Generalitat de Catalunya
- Ministerio de Economía y Competitividad
- Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares
- HORIZON EUROPE Framework Programme
- Instituto de Salud Carlos III
- European Regional Development Fund