Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium

被引：23

作者：

Cokic, Ivan ^{[1
]}

Chan, Shing Fai ^{[2
]}

Guan, Xingmin ^{[2
]}

Nair, Anand R. ^{[1
]}

Yang, Hsin-Jung ^{[1
]}

Liu, Ting ^{[1
]}

Chen, Yinyin ^{[1
]}

Hernando, Diego ^{[3
]}

Sykes, Jane ^{[4
]}

Tang, Richard ^{[2
]}

Butler, John ^{[4
]}

Dohnalkova, Alice ^{[5
]}

Kovarik, Libor ^{[5
]}

Finney, Robert ^{[6
]}

Kali, Avinash ^{[1
]}

Sharif, Behzad ^{[2
]}

Bouchard, Louis S. ^{[7
]}

Gupta, Rajesh ^{[8
]}

Krishnam, Mayil Singaram ^{[9
]}

Vora, Keyur ^{[2
]}

Tamarappoo, Balaji ^{[2
]}

Howarth, Andrew G. ^{[10
]}

Kumar, Andreas ^{[11
]}

Francis, Joseph ^{[12
]}

Reeder, Scott B. ^{[3
]}

Wood, John C. ^{[13
]}

Prato, Frank S. ^{[4
]}

Dharmakumar, Rohan ^{[2
]}

机构：

[1] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[2] Indiana Univ Sch Med, Krannert Cardiovasc Res Ctr, IU Hlth Cardiovasc Inst, Indianapolis, IN 46202 USA

[3] Univ Wisconsin, Madison, WI USA

[4] Univ Western Ontario, Lawson Hlth Res Inst, London, ON, Canada

[5] Pacific Northwest Natl Lab, Richland, WA 99352 USA

[6] Cardiotheranostics, Los Angeles, CA USA

[7] Univ Calif Los Angeles, Los Angeles, CA USA

[8] Univ Toledo, 2801 W Bancroft St, Toledo, OH 43606 USA

[9] Stanford Univ, Palo Alto, CA 94304 USA

[10] Univ Calgary, Calgary, AB, Canada

[11] Northern Ontario Sch Med, Sudbury, ON, Canada

[12] Louisiana State Univ, Baton Rouge, LA 70803 USA

[13] Univ Southern Calif, Los Angeles, CA 90007 USA

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

关键词：

CIRCUMFERENTIAL STRAIN; MAGNETIC-RESONANCE; IRON; MACROPHAGES; METABOLISM; INJURY; ACTIVATION; MECHANISMS; CHELATION; OXIDATION;

D O I：

10.1038/s41467-022-33776-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. It is unclear why hemorrhagic myocardial infarctions (hMI) are destined for adverse outcomes. Here, the authors show that hMI drives fatty degeneration of infarct territories and contributes to adverse remodeling of the heart, which can be mitigated via timely depletion of iron within the hMI zone.

引用

页数：18

共 47 条

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