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 (Institut d'Investigació Biomèdica Sant Pau)
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 Agencia Estatal de Investigación 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

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats