Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Haubner, Bernhard Johannes, Adamowicz-Brice, Martyna, Khadayate, Sanjay, Tiefenthaler, Viktoria, Metzler, Bernhard, Aitman, Tim, Penninger, Josef M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615162/
https://www.ncbi.nlm.nih.gov/pubmed/23425860
_version_ 1782264977988517888
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
work_keys_str_mv AT haubnerbernhardjohannes completecardiacregenerationinamousemodelofmyocardialinfarction
AT adamowiczbricemartyna completecardiacregenerationinamousemodelofmyocardialinfarction
AT khadayatesanjay completecardiacregenerationinamousemodelofmyocardialinfarction
AT tiefenthalerviktoria completecardiacregenerationinamousemodelofmyocardialinfarction
AT metzlerbernhard completecardiacregenerationinamousemodelofmyocardialinfarction
AT aitmantim completecardiacregenerationinamousemodelofmyocardialinfarction
AT penningerjosefm completecardiacregenerationinamousemodelofmyocardialinfarction