Next-generation sequencing reveals genetic differences between two distinct etiologies of dilated cardiomyopathy

1. Bonet, F.
2. Villa, E. Alonso
3. Hernandez-Torres, F.
4. Campanario, I.
5. Perez-Perez, C.
6. Bermudez, A.
7. Daroca, T.
8. Ranea, J.A.
9. Caballero, J. Cordoba
10. Mangas, A.
11. Toro, R.

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DOI: 10.1016/J.ATHEROSCLEROSIS.2023.06.601 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Atherosclerosis

Resumen

Background and Aims: Dilated cardiomyopathy (DCM) entails a broad group of diseases, acquired or genetic, which result in a similar phenotype. In the era of precision medicine, genotype-directed therapies have started to emerge. MicroRNAs (miRNAs) are short sequences of non-coding RNA that play an important role in the regulation of gene expression. MiRNAs are crucial in the development of several cardiovascular diseases, including DCM. The aim of this study was to analyze the mRNA and miRNA transcriptome in human heart tissue to delineate DCM etiology-specific gene expression signatures.Methods: We used miRNA and mRNA sequencing to identify differences between the transcriptome of human left vetricular (LV) tissue from patients with DCM caused by volume overload (DCMv) and ischemic DCM (ICM). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the differentially expressed genes. Diferentially expressed miRNAs were validated by qRT-PCR.Results: MiRNome and transcriptome of human LV tissue showed 111 mRNAs and 5 miRNAs dysregulated in DCMv vs ICM, and unveiled 37 miRNA-mRNA interactions. GO analysis revealed extracellular matrix pathways among the most enriched GO terms. KEGG pathway revealed cardiac muscle contraction, calcium signaling, fatty acid and immune response among the most enriched pathways. Finally, qRT-PCR validation in all collected DCMv (n = 8) and ICM (n = 5) samples showed that miR-218-5p, miR-487b-3p and miR-494-3p are upregulated in DCMv as compared to ICM.Conclusions: Our results suggest that transcriptome signatures may distinguish distinct etiologies of DCM, shedding light on underlying biological differences between DCMv and ICM.