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Systems Biology in Chronic Heart Failure—Identification of Potential miRNA Regulators

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 sy...

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Autores principales: Vilella-Figuerola, Alba, Gallinat, Alex, Escate, Rafael, Mirabet, Sònia, Padró, Teresa, Badimon, Lina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740605/
https://www.ncbi.nlm.nih.gov/pubmed/36499552
http://dx.doi.org/10.3390/ijms232315226
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author Vilella-Figuerola, Alba
Gallinat, Alex
Escate, Rafael
Mirabet, Sònia
Padró, Teresa
Badimon, Lina
author_facet Vilella-Figuerola, Alba
Gallinat, Alex
Escate, Rafael
Mirabet, Sònia
Padró, Teresa
Badimon, Lina
author_sort Vilella-Figuerola, Alba
collection PubMed
description 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.
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spelling pubmed-97406052022-12-11 Systems Biology in Chronic Heart Failure—Identification of Potential miRNA Regulators Vilella-Figuerola, Alba Gallinat, Alex Escate, Rafael Mirabet, Sònia Padró, Teresa Badimon, Lina Int J Mol Sci Article 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. MDPI 2022-12-03 /pmc/articles/PMC9740605/ /pubmed/36499552 http://dx.doi.org/10.3390/ijms232315226 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vilella-Figuerola, Alba
Gallinat, Alex
Escate, Rafael
Mirabet, Sònia
Padró, Teresa
Badimon, Lina
Systems Biology in Chronic Heart Failure—Identification of Potential miRNA Regulators
title Systems Biology in Chronic Heart Failure—Identification of Potential miRNA Regulators
title_full Systems Biology in Chronic Heart Failure—Identification of Potential miRNA Regulators
title_fullStr Systems Biology in Chronic Heart Failure—Identification of Potential miRNA Regulators
title_full_unstemmed Systems Biology in Chronic Heart Failure—Identification of Potential miRNA Regulators
title_short Systems Biology in Chronic Heart Failure—Identification of Potential miRNA Regulators
title_sort systems biology in chronic heart failure—identification of potential mirna regulators
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740605/
https://www.ncbi.nlm.nih.gov/pubmed/36499552
http://dx.doi.org/10.3390/ijms232315226
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