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Complete cardiac regeneration in a mouse model of myocardial infarction
Cardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, complete cardiac regeneration has been demonstrated in fish and newborn mice following resection of the cardiac apex. However, it remain...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615162/ https://www.ncbi.nlm.nih.gov/pubmed/23425860 |
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author | Haubner, Bernhard Johannes Adamowicz-Brice, Martyna Khadayate, Sanjay Tiefenthaler, Viktoria Metzler, Bernhard Aitman, Tim Penninger, Josef M. |
author_facet | Haubner, Bernhard Johannes Adamowicz-Brice, Martyna Khadayate, Sanjay Tiefenthaler, Viktoria Metzler, Bernhard Aitman, Tim Penninger, Josef M. |
author_sort | Haubner, Bernhard Johannes |
collection | PubMed |
description | Cardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, complete cardiac regeneration has been demonstrated in fish and newborn mice following resection of the cardiac apex. However, it remained entirely unclear whether the mammalian heart can also completely regenerate following a complex cardiac ischemic injury. We established a protocol to induce a severe heart attack in one-day-old mice using left anterior descending artery (LAD) ligation. LAD ligation triggered substantial cardiac injury in the left ventricle defined by Caspase 3 activation and massive cell death. Ischemia-induced cardiomyocyte death was also visible on day 4 after LAD ligation. Remarkably, 7 days after the initial ischemic insult, we observed complete cardiac regeneration without any signs of tissue damage or scarring. This tissue regeneration translated into long-term normal heart functions as assessed by echocardiography. In contrast, LAD ligations in 7-day-old mice resulted in extensive scarring comparable to adult mice, indicating that the regenerative capacity for complete cardiac healing after heart attacks can be traced to the first week after birth. RNAseq analyses of hearts on day 1, day 3, and day 10 and comparing LAD-ligated and sham-operated mice surprisingly revealed a transcriptional programme of major changes in genes mediating mitosis and cell division between days 1, 3 and 10 postnatally and a very limited set of genes, including genes regulating cell cycle and extracellular matrix synthesis, being differentially regulated in the regenerating hearts. We present for the first time a mammalian model of complete cardiac regeneration following a severe ischemic cardiac injury. This novel model system provides the unique opportunity to uncover molecular and cellular pathways that can induce cardiac regeneration after ischemic injury, findings that one day could be translated to human heart attack patients. |
format | Online Article Text |
id | pubmed-3615162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-36151622013-04-05 Complete cardiac regeneration in a mouse model of myocardial infarction Haubner, Bernhard Johannes Adamowicz-Brice, Martyna Khadayate, Sanjay Tiefenthaler, Viktoria Metzler, Bernhard Aitman, Tim Penninger, Josef M. Aging (Albany NY) Research Paper Cardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, complete cardiac regeneration has been demonstrated in fish and newborn mice following resection of the cardiac apex. However, it remained entirely unclear whether the mammalian heart can also completely regenerate following a complex cardiac ischemic injury. We established a protocol to induce a severe heart attack in one-day-old mice using left anterior descending artery (LAD) ligation. LAD ligation triggered substantial cardiac injury in the left ventricle defined by Caspase 3 activation and massive cell death. Ischemia-induced cardiomyocyte death was also visible on day 4 after LAD ligation. Remarkably, 7 days after the initial ischemic insult, we observed complete cardiac regeneration without any signs of tissue damage or scarring. This tissue regeneration translated into long-term normal heart functions as assessed by echocardiography. In contrast, LAD ligations in 7-day-old mice resulted in extensive scarring comparable to adult mice, indicating that the regenerative capacity for complete cardiac healing after heart attacks can be traced to the first week after birth. RNAseq analyses of hearts on day 1, day 3, and day 10 and comparing LAD-ligated and sham-operated mice surprisingly revealed a transcriptional programme of major changes in genes mediating mitosis and cell division between days 1, 3 and 10 postnatally and a very limited set of genes, including genes regulating cell cycle and extracellular matrix synthesis, being differentially regulated in the regenerating hearts. We present for the first time a mammalian model of complete cardiac regeneration following a severe ischemic cardiac injury. This novel model system provides the unique opportunity to uncover molecular and cellular pathways that can induce cardiac regeneration after ischemic injury, findings that one day could be translated to human heart attack patients. Impact Journals LLC 2012-12-31 /pmc/articles/PMC3615162/ /pubmed/23425860 Text en Copyright: © 2012 Haubner et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Paper Haubner, Bernhard Johannes Adamowicz-Brice, Martyna Khadayate, Sanjay Tiefenthaler, Viktoria Metzler, Bernhard Aitman, Tim Penninger, Josef M. Complete cardiac regeneration in a mouse model of myocardial infarction |
title | Complete cardiac regeneration in a mouse model of myocardial infarction |
title_full | Complete cardiac regeneration in a mouse model of myocardial infarction |
title_fullStr | Complete cardiac regeneration in a mouse model of myocardial infarction |
title_full_unstemmed | Complete cardiac regeneration in a mouse model of myocardial infarction |
title_short | Complete cardiac regeneration in a mouse model of myocardial infarction |
title_sort | complete cardiac regeneration in a mouse model of myocardial infarction |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615162/ https://www.ncbi.nlm.nih.gov/pubmed/23425860 |
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