Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium

dc.contributor.authorCokic, Ivan
dc.contributor.authorChan, Shing Fai
dc.contributor.authorGuan, Xingmin
dc.contributor.authorNair, Anand R.
dc.contributor.authorYang, Hsin-Jung
dc.contributor.authorLiu, Ting
dc.contributor.authorChen, Yinyin
dc.contributor.authorHernando, Diego
dc.contributor.authorSykes, Jane
dc.contributor.authorTang, Richard
dc.contributor.authorButler, John
dc.contributor.authorDohnalkova, Alice
dc.contributor.authorKovarik, Libor
dc.contributor.authorFinney, Robert
dc.contributor.authorKali, Avinash
dc.contributor.authorSharif, Behzad
dc.contributor.authorBouchard, Louis S.
dc.contributor.authorGupta, Rajesh
dc.contributor.authorKrishnam, Mayil Singaram
dc.contributor.authorVora, Keyur
dc.contributor.authorTamarappoo, Balaji
dc.contributor.authorHowarth, Andrew G.
dc.contributor.authorKumar, Andreas
dc.contributor.authorFrancis, Joseph
dc.contributor.authorReeder, Scott B.
dc.contributor.authorWood, John C.
dc.contributor.authorPrato, Frank S.
dc.contributor.authorDharmakumar, Rohan
dc.contributor.departmentMedicine, School of Medicine
dc.description.abstractSudden 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.
dc.eprint.versionFinal published version
dc.identifier.citationCokic I, Chan SF, Guan X, et al. Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium. Nat Commun. 2022;13(1):6394. Published 2022 Oct 27. doi:10.1038/s41467-022-33776-x
dc.publisherSpringer Nature
dc.relation.journalNature Communications
dc.rightsAttribution 4.0 Internationalen
dc.subjectTranslational research
dc.subjectHeart failure
dc.titleIntramyocardial hemorrhage drives fatty degeneration of infarcted myocardium
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