Tenascin‐C aggravates ventricular dilatation and angiotensin‐converting enzyme activity after myocardial infarction in mice
Abstract Aims Tenascin‐C (TN‐C) is suggested to be detrimental in cardiac remodelling after myocardial infarction (MI). The aim of this study is to reveal the effects of TN‐C on extracellular matrix organization and its haemodynamic influence in an experimental mouse model of MI and in myocardial ce...
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Format: | Article |
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Wiley
2020-10-01
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Series: | ESC Heart Failure |
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Online Access: | https://doi.org/10.1002/ehf2.12794 |
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doaj-91ad737678b74223b8fd980be7256afe |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David Santer Felix Nagel Inês Fonseca Gonçalves Christoph Kaun Johann Wojta Miklós Fagyas Martin Krššák Ágnes Balogh Zoltán Papp Attila Tóth Viktor Bánhegyi Karola Trescher Attila Kiss Bruno K. Podesser |
spellingShingle |
David Santer Felix Nagel Inês Fonseca Gonçalves Christoph Kaun Johann Wojta Miklós Fagyas Martin Krššák Ágnes Balogh Zoltán Papp Attila Tóth Viktor Bánhegyi Karola Trescher Attila Kiss Bruno K. Podesser Tenascin‐C aggravates ventricular dilatation and angiotensin‐converting enzyme activity after myocardial infarction in mice ESC Heart Failure Tenascin‐C Heart failure Myocardial infarction Isolated working heart Mouse model Extracellular matrix |
author_facet |
David Santer Felix Nagel Inês Fonseca Gonçalves Christoph Kaun Johann Wojta Miklós Fagyas Martin Krššák Ágnes Balogh Zoltán Papp Attila Tóth Viktor Bánhegyi Karola Trescher Attila Kiss Bruno K. Podesser |
author_sort |
David Santer |
title |
Tenascin‐C aggravates ventricular dilatation and angiotensin‐converting enzyme activity after myocardial infarction in mice |
title_short |
Tenascin‐C aggravates ventricular dilatation and angiotensin‐converting enzyme activity after myocardial infarction in mice |
title_full |
Tenascin‐C aggravates ventricular dilatation and angiotensin‐converting enzyme activity after myocardial infarction in mice |
title_fullStr |
Tenascin‐C aggravates ventricular dilatation and angiotensin‐converting enzyme activity after myocardial infarction in mice |
title_full_unstemmed |
Tenascin‐C aggravates ventricular dilatation and angiotensin‐converting enzyme activity after myocardial infarction in mice |
title_sort |
tenascin‐c aggravates ventricular dilatation and angiotensin‐converting enzyme activity after myocardial infarction in mice |
publisher |
Wiley |
series |
ESC Heart Failure |
issn |
2055-5822 |
publishDate |
2020-10-01 |
description |
Abstract Aims Tenascin‐C (TN‐C) is suggested to be detrimental in cardiac remodelling after myocardial infarction (MI). The aim of this study is to reveal the effects of TN‐C on extracellular matrix organization and its haemodynamic influence in an experimental mouse model of MI and in myocardial cell culture during hypoxic conditions. Methods and results Myocardial infarction was induced in TN‐C knockout (TN‐C KO) and wild‐type mice. Six weeks later, cardiac function was studied by magnetic resonance imaging and under isolated working heart conditions. Myocardial mRNA levels and immunoreactivity of TN‐C, TIMP‐1, TIMP‐3, and matrix metalloproteinase (MMP)‐9, as well as serum and tissue activities of angiotensin‐converting enzyme (ACE), were determined at 1 and 6 weeks after infarction. Cardiac output and external heart work were higher, while left ventricular wall stress and collagen expression were decreased (P < 0.05) in TN‐C KO mice as compared with age‐matched controls at 6 weeks after infarction. TIMP‐1 expression was down‐regulated at 1 and 6 weeks, and TIMP‐3 expression was up‐regulated at 1 week (P < 0.01) after infarction in knockout mice. MMP‐9 level was lower in TN‐C KO at 6 weeks after infarction (P < 0.05). TIMP‐3/MMP‐9 ratio was higher in knockout mice at 1 and 6 weeks after infarction (P < 0.01). ACE activity in the myocardial border zone (i.e. between scar and free wall) was significantly lower in knockout than in wild‐type mice 1 week after MI (P < 0.05). Conclusions Tenascin‐C expression is induced by hypoxia in association with ACE activity and MMP‐2 and MMP‐9 elevations, thereby promoting left ventricular dilatation after MI. |
topic |
Tenascin‐C Heart failure Myocardial infarction Isolated working heart Mouse model Extracellular matrix |
url |
https://doi.org/10.1002/ehf2.12794 |
work_keys_str_mv |
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doaj-91ad737678b74223b8fd980be7256afe2021-06-02T08:45:53ZengWileyESC Heart Failure2055-58222020-10-01752113212210.1002/ehf2.12794Tenascin‐C aggravates ventricular dilatation and angiotensin‐converting enzyme activity after myocardial infarction in miceDavid Santer0Felix Nagel1Inês Fonseca Gonçalves2Christoph Kaun3Johann Wojta4Miklós Fagyas5Martin Krššák6Ágnes Balogh7Zoltán Papp8Attila Tóth9Viktor Bánhegyi10Karola Trescher11Attila Kiss12Bruno K. Podesser13Ludwig Boltzmann Institute for Cardiovascular Research Medical University of Vienna Waehringer Guertel 18‐20, 1Q Vienna 1090 AustriaLudwig Boltzmann Institute for Cardiovascular Research Medical University of Vienna Waehringer Guertel 18‐20, 1Q Vienna 1090 AustriaLudwig Boltzmann Institute for Cardiovascular Research Medical University of Vienna Waehringer Guertel 18‐20, 1Q Vienna 1090 AustriaDepartment of Internal Medicine II, Division of Cardiology Medical University of Vienna Vienna AustriaLudwig Boltzmann Institute for Cardiovascular Research Medical University of Vienna Waehringer Guertel 18‐20, 1Q Vienna 1090 AustriaDivision of Clinical Physiology, Department of Cardiology, Research Centre for Molecular Medicine, Faculty of Medicine University of Debrecen Debrecen HungaryDepartment of Internal Medicine III, Division of Endocrinology and Metabolism Medical University of Vienna Vienna AustriaDivision of Clinical Physiology, Department of Cardiology, Research Centre for Molecular Medicine, Faculty of Medicine University of Debrecen Debrecen HungaryDivision of Clinical Physiology, Department of Cardiology, Research Centre for Molecular Medicine, Faculty of Medicine University of Debrecen Debrecen HungaryDivision of Clinical Physiology, Department of Cardiology, Research Centre for Molecular Medicine, Faculty of Medicine University of Debrecen Debrecen HungaryDivision of Clinical Physiology, Department of Cardiology, Research Centre for Molecular Medicine, Faculty of Medicine University of Debrecen Debrecen HungaryLudwig Boltzmann Institute for Cardiovascular Research Medical University of Vienna Waehringer Guertel 18‐20, 1Q Vienna 1090 AustriaLudwig Boltzmann Institute for Cardiovascular Research Medical University of Vienna Waehringer Guertel 18‐20, 1Q Vienna 1090 AustriaLudwig Boltzmann Institute for Cardiovascular Research Medical University of Vienna Waehringer Guertel 18‐20, 1Q Vienna 1090 AustriaAbstract Aims Tenascin‐C (TN‐C) is suggested to be detrimental in cardiac remodelling after myocardial infarction (MI). The aim of this study is to reveal the effects of TN‐C on extracellular matrix organization and its haemodynamic influence in an experimental mouse model of MI and in myocardial cell culture during hypoxic conditions. Methods and results Myocardial infarction was induced in TN‐C knockout (TN‐C KO) and wild‐type mice. Six weeks later, cardiac function was studied by magnetic resonance imaging and under isolated working heart conditions. Myocardial mRNA levels and immunoreactivity of TN‐C, TIMP‐1, TIMP‐3, and matrix metalloproteinase (MMP)‐9, as well as serum and tissue activities of angiotensin‐converting enzyme (ACE), were determined at 1 and 6 weeks after infarction. Cardiac output and external heart work were higher, while left ventricular wall stress and collagen expression were decreased (P < 0.05) in TN‐C KO mice as compared with age‐matched controls at 6 weeks after infarction. TIMP‐1 expression was down‐regulated at 1 and 6 weeks, and TIMP‐3 expression was up‐regulated at 1 week (P < 0.01) after infarction in knockout mice. MMP‐9 level was lower in TN‐C KO at 6 weeks after infarction (P < 0.05). TIMP‐3/MMP‐9 ratio was higher in knockout mice at 1 and 6 weeks after infarction (P < 0.01). ACE activity in the myocardial border zone (i.e. between scar and free wall) was significantly lower in knockout than in wild‐type mice 1 week after MI (P < 0.05). Conclusions Tenascin‐C expression is induced by hypoxia in association with ACE activity and MMP‐2 and MMP‐9 elevations, thereby promoting left ventricular dilatation after MI.https://doi.org/10.1002/ehf2.12794Tenascin‐CHeart failureMyocardial infarctionIsolated working heartMouse modelExtracellular matrix |