Cardiac protection by pirfenidone after myocardial infarction: a bioinformatic analysis.

Animals Computational Biology Fibrosis Myocardial Infarction / metabolism Myocardium / metabolism Pyridones / metabolism Swine Ventricular Function, Left Ventricular Remodeling

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
18 03 2022
Historique:
received: 02 10 2021
accepted: 28 02 2022
entrez: 19 3 2022
pubmed: 20 3 2022
medline: 6 5 2022
Statut: epublish

Résumé

Left ventricular (LV) remodeling after myocardial infarction (MI) is promoted by an intense fibrotic response, which could be targeted by the anti-fibrotic drug pirfenidone. We explored the relationship between protein modulation by pirfenidone and post-MI remodeling, based on molecular information and transcriptomic data from a swine model of MI. We identified 6 causative motives of post-MI remodeling (cardiomyocyte cell death, impaired myocyte contractility, extracellular matrix remodeling and fibrosis, hypertrophy, renin-angiotensin-aldosterone system activation, and inflammation), 4 pirfenidone targets and 21 bioflags (indirect effectors). Pirfenidone had a more widespread action than gold-standard drugs, encompassing all 6 motives, with prominent effects on p38γ-MAPK12, the TGFβ1-SMAD2/3 pathway and other effector proteins such as matrix metalloproteases 2 and 14, PDGFA/B, and IGF1. A bioinformatic approach allowed to identify several possible mechanisms of action of pirfenidone with beneficial effects in the post-MI LV remodeling, and suggests additional effects over guideline-recommended therapies.

Identifiants

DOI: 10.1038/s41598-022-08523-3 PMID: 35304529 PMC: PMC8933518
pubmed: 35304529
doi: 10.1038/s41598-022-08523-3
pii: 10.1038/s41598-022-08523-3
pmc: PMC8933518
doi:

Substances chimiques

Pyridones 0
pirfenidone D7NLD2JX7U

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

4691

Informations de copyright

© 2022. The Author(s).

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Auteurs

Alberto Aimo (A)

Institute of Life Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy. a.aimo@santannapisa.it.
Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy. a.aimo@santannapisa.it.

Oriol Iborra-Egea (O)

ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Health Sciences Research Institute Germans Trias I Pujol (IGTP), Barcelona, Spain.
CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.

Nicola Martini (N)

Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

Carolina Galvez-Monton (C)

ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Health Sciences Research Institute Germans Trias I Pujol (IGTP), Barcelona, Spain.

Silvia Burchielli (S)

Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

Giorgia Panichella (G)

Institute of Life Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy.

Claudio Passino (C)

Institute of Life Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy.
Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

Michele Emdin (M)

Institute of Life Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy.
Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

Antoni Bayes-Genis (A)

ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Health Sciences Research Institute Germans Trias I Pujol (IGTP), Barcelona, Spain.
CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Cardiac protection by pirfenidone after...
questionsmedicales.fr › Sciences de l'information › Informatique › Biologie informatique › Cardiac protection by pirfenidone after...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Cardiac protection by pirfenidone after...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Nécrose › Infarctus › Infarctus du myocarde › Cardiac protection by pirfenidone after...
questionsmedicales.fr › Tissus › Muscles › Muscle strié › Myocarde › Cardiac protection by pirfenidone after...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Pyridones › Cardiac protection by pirfenidone after...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Artiodactyla › Suidae › Cardiac protection by pirfenidone after...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Fonction ventriculaire › Fonction ventriculaire gauche › Cardiac protection by pirfenidone after...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Fonction ventriculaire › Remodelage ventriculaire › Cardiac protection by pirfenidone after...