Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 10 2022
27 10 2022
Historique:
received:
31
10
2020
accepted:
03
10
2022
entrez:
27
10
2022
pubmed:
28
10
2022
medline:
1
11
2022
Statut:
epublish
Résumé
Sudden blockage of arteries supplying the heart muscle contributes to millions of heart attacks (myocardial infarction, MI) around the world. Although re-opening these arteries (reperfusion) saves MI patients from immediate death, approximately 50% of these patients go on to develop chronic heart failure (CHF) and die within a 5-year period; however, why some patients accelerate towards CHF while others do not remains unclear. Here we show, using large animal models of reperfused MI, that intramyocardial hemorrhage - the most damaging form of reperfusion injury (evident in nearly 40% of reperfused ST-elevation MI patients) - drives delayed infarct healing and is centrally responsible for continuous fatty degeneration of the infarcted myocardium contributing to adverse remodeling of the heart. Specifically, we show that the fatty degeneration of the hemorrhagic MI zone stems from iron-induced macrophage activation, lipid peroxidation, foam cell formation, ceroid production, foam cell apoptosis and iron recycling. We also demonstrate that timely reduction of iron within the hemorrhagic MI zone reduces fatty infiltration and directs the heart towards favorable remodeling. Collectively, our findings elucidate why some, but not all, MIs are destined to CHF and help define a potential therapeutic strategy to mitigate post-MI CHF independent of MI size.
Identifiants
pubmed: 36302906
doi: 10.1038/s41467-022-33776-x
pii: 10.1038/s41467-022-33776-x
pmc: PMC9613644
doi:
Substances chimiques
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6394Subventions
Organisme : NHLBI NIH HHS
ID : R00 HL124323
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133407
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136578
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147133
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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