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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9740605 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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