Role of miRNA-mRNA Interactome in Pathophysiology of Arrhythmogenic Cardiomyopathy
Por:
Bonet, F, Campuzano, O, Cordoba-Caballero, J, Alcalde, M, Sarquella-Brugada G, Braza-Boils, A, Brugada, R, Hernandez-Torres, F, Quezada-Feijoo, M, Ramos, M, Mangas, A, Ranea, JAG and Toro, R
Publicada:
1 ago 2024
Resumen:
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-beta 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.
Filiaciones:
Bonet, F:
Puerta Mar Univ Hosp, Biomed Res & Innovat Inst Cadiz INiB, Res Unit, Cadiz 11009, Spain
Campuzano, O:
Univ Girona, Sch Med, Med Sci Dept, Girona 17003, Spain
Inst Invest Biomed Girona IDIBGI CERCA, Salt 17190, Spain
Ctr Invest Biomed Red Enfermedades Cardiovasc CIBE, Madrid 28029, Spain
Cordoba-Caballero, J:
Puerta Mar Univ Hosp, Biomed Res & Innovat Inst Cadiz INiB, Res Unit, Cadiz 11009, Spain
Univ Malaga, Dept Mol Biol & Biochem, Malaga 29071, Spain
Alcalde, M:
Inst Invest Biomed Girona IDIBGI CERCA, Salt 17190, Spain
Ctr Invest Biomed Red Enfermedades Cardiovasc CIBE, Madrid 28029, Spain
Sarquella-Brugada G:
Univ Girona, Sch Med, Med Sci Dept, Girona 17003, Spain
St Joan Deu Hosp, Cardiol Dept, Inherited Cardiac Dis & Sudden Death Unit, Pediat Arrhythmias, Barcelona 08950, Spain
Inst Recerca St Joan Deu, Arritmies Pediat Cardiol Genet & Mort Sobtada Mala, Barcelona 08950, Spain
Braza-Boils, A:
Ctr Invest Biomed Red Enfermedades Cardiovasc CIBE, Madrid 28029, Spain
Inst Invest Sanitaria La Fe, Cardiopatias Familiares Muerte Subita & Mecanismos, Valencia 46026, Spain
Brugada, R:
Univ Girona, Sch Med, Med Sci Dept, Girona 17003, Spain
Inst Invest Biomed Girona IDIBGI CERCA, Salt 17190, Spain
Ctr Invest Biomed Red Enfermedades Cardiovasc CIBE, Madrid 28029, Spain
Hosp Josep Trueta Girona, Cardiol Serv, Girona 17007, Spain
Hernandez-Torres, F:
Technol Pk Hlth Sci, Medina Fdn, Granada 18016, Spain
Univ Granada, Fac Med, Dept Biochem & Mol Biologyand Immunol 3, Granada 18016, Spain
Quezada-Feijoo, M:
Hosp Cent Cruz Roja, Cardiol Dept, Madrid 28003, Spain
Alfonso X Sabio Univ, Med Sch, Madrid 28007, Spain
Ramos, M:
Hosp Cent Cruz Roja, Cardiol Dept, Madrid 28003, Spain
Alfonso X Sabio Univ, Med Sch, Madrid 28007, Spain
Mangas, A:
Puerta Mar Univ Hosp, Biomed Res & Innovat Inst Cadiz INiB, Res Unit, Cadiz 11009, Spain
Univ Cadiz, Sch Med, Med Dept, Cadiz 11003, Spain
Puerta Mar Univ Hosp, Lipid & Atherosclerot Unit, Cadiz 11009, Spain
Ranea, JAG:
Univ Malaga, Dept Mol Biol & Biochem, Malaga 29071, Spain
Inst Biomed Res Malaga & platform Nanomed IBIMA Pl, Malaga 29071, Spain
Inst Salud Carlos III ISCIII, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain
Inst Salud Carlos III ISCIII, Spanish Natl Bioinformat Inst INB ELIXIR ES, Madrid 28020, Spain
Toro, R:
Puerta Mar Univ Hosp, Biomed Res & Innovat Inst Cadiz INiB, Res Unit, Cadiz 11009, Spain
Univ Cadiz, Sch Med, Med Dept, Cadiz 11003, Spain
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