Systems Biology in Chronic Heart Failure-Identification of Potential miRNA Regulators
Vilella-Figuerola, Alba (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Gallinat, Alex (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Escate, Rafael (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Mirabet Pérez, Sonia (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Padró, Teresa (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)

Data:	2022
Resum:	Heart failure (HF) is a complex disease entity with high clinical impact, poorly understood pathophysiology and scantly known miRNA-mediated epigenetic regulation. We have analysed miRNA patterns in patients with chronic HF (cHF) and a sex- and age-matched reference group and pursued an in silico system biology analysis to discern pathways involved in cHF pathophysiology. Twenty-eight miRNAs were identified in cHF that were up-regulated in the reference group, and eight of them were validated by RT-qPCR. In silico analysis of predicted targets by STRING protein-protein interaction networks revealed eight cluster networks (involving seven of the identified miRNAs) enriched in pathways related to cell cycle, Ras, chemokine, PI3K-AKT and TGF-β signaling. By ROC curve analysis, combined probabilities of these seven miRNAs (let-7a-5p, miR-107, miR-125a-5p, miR-139-5p, miR-150-5p, miR-30b-5p and miR-342-3p ; clusters 1-4 [C:1-4]), discriminated between HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), and ischaemic and non-ischaemic aetiology. A combination of miR-107, miR-139-5p and miR-150-5p, involved in clusters 5 and 7 (C:5+7), discriminated HFpEF from HFrEF. Pathway enrichment analysis of miRNAs present in C:1-4 (let-7a-5p, miR-125a-5p, miR-30b-5p and miR-342-3p) revealed pathways related to HF pathogenesis. In conclusion, we have identified a differential signature of down-regulated miRNAs in the plasma of HF patients and propose novel cellular mechanisms involved in cHF pathogenesis.
Ajuts:	Agencia Estatal de Investigación PID2019-107160RB-I00 Instituto de Salud Carlos III PI19/01687 Instituto de Salud Carlos III RD21/0017/0013 European Commission 821283 Ministerio de Economía, Industria y Competitividad BES-2017-081378
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Mirna ; Chronic heart failure ; Network ; Enrichment pathways ; Pathophysiology
Publicat a:	International journal of molecular sciences, Vol. 23, Issue 23 (December 2022) , art. 15226, ISSN 1422-0067

DOI: 10.3390/ijms232315226
PMID: 36499552

22 p, 4.7 MB

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