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Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium
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 fa...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9613644/ https://www.ncbi.nlm.nih.gov/pubmed/36302906 http://dx.doi.org/10.1038/s41467-022-33776-x |
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author | Cokic, Ivan Chan, Shing Fai Guan, Xingmin Nair, Anand R. Yang, Hsin-Jung Liu, Ting Chen, Yinyin Hernando, Diego Sykes, Jane Tang, Richard Butler, John Dohnalkova, Alice Kovarik, Libor Finney, Robert Kali, Avinash Sharif, Behzad Bouchard, Louis S. Gupta, Rajesh Krishnam, Mayil Singaram Vora, Keyur Tamarappoo, Balaji Howarth, Andrew G. Kumar, Andreas Francis, Joseph Reeder, Scott B. Wood, John C. Prato, Frank S. Dharmakumar, Rohan |
author_facet | Cokic, Ivan Chan, Shing Fai Guan, Xingmin Nair, Anand R. Yang, Hsin-Jung Liu, Ting Chen, Yinyin Hernando, Diego Sykes, Jane Tang, Richard Butler, John Dohnalkova, Alice Kovarik, Libor Finney, Robert Kali, Avinash Sharif, Behzad Bouchard, Louis S. Gupta, Rajesh Krishnam, Mayil Singaram Vora, Keyur Tamarappoo, Balaji Howarth, Andrew G. Kumar, Andreas Francis, Joseph Reeder, Scott B. Wood, John C. Prato, Frank S. Dharmakumar, Rohan |
author_sort | Cokic, Ivan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9613644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96136442022-10-29 Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium Cokic, Ivan Chan, Shing Fai Guan, Xingmin Nair, Anand R. Yang, Hsin-Jung Liu, Ting Chen, Yinyin Hernando, Diego Sykes, Jane Tang, Richard Butler, John Dohnalkova, Alice Kovarik, Libor Finney, Robert Kali, Avinash Sharif, Behzad Bouchard, Louis S. Gupta, Rajesh Krishnam, Mayil Singaram Vora, Keyur Tamarappoo, Balaji Howarth, Andrew G. Kumar, Andreas Francis, Joseph Reeder, Scott B. Wood, John C. Prato, Frank S. Dharmakumar, Rohan Nat Commun Article 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. Nature Publishing Group UK 2022-10-27 /pmc/articles/PMC9613644/ /pubmed/36302906 http://dx.doi.org/10.1038/s41467-022-33776-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Cokic, Ivan Chan, Shing Fai Guan, Xingmin Nair, Anand R. Yang, Hsin-Jung Liu, Ting Chen, Yinyin Hernando, Diego Sykes, Jane Tang, Richard Butler, John Dohnalkova, Alice Kovarik, Libor Finney, Robert Kali, Avinash Sharif, Behzad Bouchard, Louis S. Gupta, Rajesh Krishnam, Mayil Singaram Vora, Keyur Tamarappoo, Balaji Howarth, Andrew G. Kumar, Andreas Francis, Joseph Reeder, Scott B. Wood, John C. Prato, Frank S. Dharmakumar, Rohan Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium |
title | Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium |
title_full | Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium |
title_fullStr | Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium |
title_full_unstemmed | Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium |
title_short | Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium |
title_sort | intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9613644/ https://www.ncbi.nlm.nih.gov/pubmed/36302906 http://dx.doi.org/10.1038/s41467-022-33776-x |
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