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Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice

We have previously demonstrated that adult transgenic C57BL/6J mice with CM-restricted overexpression of the dominant negative W(v) mutant protein (dn-c-kit-Tg) respond to pressure overload with robust cardiomyocyte (CM) cell cycle entry. Here, we tested if outcomes after myocardial infarction (MI)...

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Autores principales: Iismaa, Siiri E., Li, Ming, Kesteven, Scott, Wu, Jianxin, Chan, Andrea Y., Holman, Sara R., Calvert, John W., Haq, Ahtesham ul, Nicks, Amy M., Naqvi, Nawazish, Husain, Ahsan, Feneley, Michael P., Graham, Robert M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904135/
https://www.ncbi.nlm.nih.gov/pubmed/29666426
http://dx.doi.org/10.1038/s41598-018-24525-6
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author Iismaa, Siiri E.
Li, Ming
Kesteven, Scott
Wu, Jianxin
Chan, Andrea Y.
Holman, Sara R.
Calvert, John W.
Haq, Ahtesham ul
Nicks, Amy M.
Naqvi, Nawazish
Husain, Ahsan
Feneley, Michael P.
Graham, Robert M.
author_facet Iismaa, Siiri E.
Li, Ming
Kesteven, Scott
Wu, Jianxin
Chan, Andrea Y.
Holman, Sara R.
Calvert, John W.
Haq, Ahtesham ul
Nicks, Amy M.
Naqvi, Nawazish
Husain, Ahsan
Feneley, Michael P.
Graham, Robert M.
author_sort Iismaa, Siiri E.
collection PubMed
description We have previously demonstrated that adult transgenic C57BL/6J mice with CM-restricted overexpression of the dominant negative W(v) mutant protein (dn-c-kit-Tg) respond to pressure overload with robust cardiomyocyte (CM) cell cycle entry. Here, we tested if outcomes after myocardial infarction (MI) due to coronary artery ligation are improved in this transgenic model. Compared to non-transgenic littermates (NTLs), adult male dn-c-kit-Tg mice displayed CM hypertrophy and concentric left ventricular (LV) hypertrophy in the absence of an increase in workload. Stroke volume and cardiac output were preserved and LV wall stress was markedly lower than that in NTLs, leading to a more energy-efficient heart. In response to MI, infarct size in adult (16-week old) dn-c-kit-Tg hearts was similar to that of NTL after 24 h but was half that in NTL hearts 12 weeks post-MI. Cumulative CM cell cycle entry was only modestly increased in dn-c-kit-Tg hearts. However, dn-c-kit-Tg mice were more resistant to infarct expansion, adverse LV remodelling and contractile dysfunction, and suffered no early death from LV rupture, relative to NTL mice. Thus, pre-existing cardiac hypertrophy lowers wall stress in dn-c-kit-Tg hearts, limits infarct expansion and prevents death from myocardial rupture.
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spelling pubmed-59041352018-04-25 Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice Iismaa, Siiri E. Li, Ming Kesteven, Scott Wu, Jianxin Chan, Andrea Y. Holman, Sara R. Calvert, John W. Haq, Ahtesham ul Nicks, Amy M. Naqvi, Nawazish Husain, Ahsan Feneley, Michael P. Graham, Robert M. Sci Rep Article We have previously demonstrated that adult transgenic C57BL/6J mice with CM-restricted overexpression of the dominant negative W(v) mutant protein (dn-c-kit-Tg) respond to pressure overload with robust cardiomyocyte (CM) cell cycle entry. Here, we tested if outcomes after myocardial infarction (MI) due to coronary artery ligation are improved in this transgenic model. Compared to non-transgenic littermates (NTLs), adult male dn-c-kit-Tg mice displayed CM hypertrophy and concentric left ventricular (LV) hypertrophy in the absence of an increase in workload. Stroke volume and cardiac output were preserved and LV wall stress was markedly lower than that in NTLs, leading to a more energy-efficient heart. In response to MI, infarct size in adult (16-week old) dn-c-kit-Tg hearts was similar to that of NTL after 24 h but was half that in NTL hearts 12 weeks post-MI. Cumulative CM cell cycle entry was only modestly increased in dn-c-kit-Tg hearts. However, dn-c-kit-Tg mice were more resistant to infarct expansion, adverse LV remodelling and contractile dysfunction, and suffered no early death from LV rupture, relative to NTL mice. Thus, pre-existing cardiac hypertrophy lowers wall stress in dn-c-kit-Tg hearts, limits infarct expansion and prevents death from myocardial rupture. Nature Publishing Group UK 2018-04-17 /pmc/articles/PMC5904135/ /pubmed/29666426 http://dx.doi.org/10.1038/s41598-018-24525-6 Text en © The Author(s) 2018 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/.
spellingShingle Article
Iismaa, Siiri E.
Li, Ming
Kesteven, Scott
Wu, Jianxin
Chan, Andrea Y.
Holman, Sara R.
Calvert, John W.
Haq, Ahtesham ul
Nicks, Amy M.
Naqvi, Nawazish
Husain, Ahsan
Feneley, Michael P.
Graham, Robert M.
Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice
title Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice
title_full Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice
title_fullStr Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice
title_full_unstemmed Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice
title_short Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice
title_sort cardiac hypertrophy limits infarct expansion after myocardial infarction in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904135/
https://www.ncbi.nlm.nih.gov/pubmed/29666426
http://dx.doi.org/10.1038/s41598-018-24525-6
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