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Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium.

ABSTRACT: 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.

SUBMITTER: Cokic I

PROVIDER: S-EPMC9613644 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium.

Cokic Ivan I Chan Shing Fai SF Guan Xingmin X Nair Anand R AR Yang Hsin-Jung HJ Liu Ting T Chen Yinyin Y Hernando Diego D Sykes Jane J Tang Richard R Butler John J Dohnalkova Alice A Kovarik Libor L Finney Robert R Kali Avinash A Sharif Behzad B Bouchard Louis S LS Gupta Rajesh R Krishnam Mayil Singaram MS Vora Keyur K Tamarappoo Balaji B Howarth Andrew G AG Kumar Andreas A Francis Joseph J Reeder Scott B SB Wood John C JC Prato Frank S FS Dharmakumar Rohan R

Nature communications 20221027 1

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 intram ...[more]

PMID: 36302906

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Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium.

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Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium.

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