Why the study?
Left ventricular remodeling after myocardial infarction is driven by an intense fibrotic response, which could potentially be targeted by the anti-fibrotic drug pirfenidone.
Does pirfenidone modulate protein pathways involved in post-myocardial infarction left ventricular remodeling?
Does pirfenidone modulate protein pathways involved in post-myocardial infarction left ventricular remodeling?
Bioinformatic analysis suggests pirfenidone may offer beneficial effects on post-MI left ventricular remodeling by targeting multiple fibrotic and inflammatory pathways, potentially providing additional benefits over guideline-recommended therapies.
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.
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Aimo et al. (2022) studied this question.
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