Iismaa, Siiri E and Li, Ming and Kesteven, Scott and Wu, Jianxin and Chan, Andrea Y and Holman, Sara R and Calvert, John W and Haq, Ahtesham Ul and Nicks, Amy M and Naqvi, Nawazish and Husain, Ahsan and Feneley, Michael P and Graham, Robert M (2018) Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice. Scientific Reports, 8 (1). p. 6114. ISSN 2045-2322 (OA)
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Abstract
We have previously demonstrated that adult transgenic C57BL/6J mice with CM-restricted overexpression of the dominant negative W 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.
| Item Type: | Article |
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| Additional Information: | 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/. |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 23 Apr 2018 22:14 |
| Last Modified: | 23 Apr 2018 22:14 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/720 |
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