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.
Original language | English |
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Pages (from-to) | 2113-2122 |
Number of pages | 10 |
Journal | ESC heart failure |
Volume | 7 |
Issue number | 5 |
DOIs | |
Publication status | Published - 01 Oct 2020 |
Keywords
- Angiotensins
- Animals
- Dilatation
- Extracellular Matrix
- Mice
- Mice, Knockout
- Myocardial Infarction/complications
- Tenascin/genetics
- Ventricular Remodeling
- Heart failure
- Myocardial infarction
- Isolated working heart
- Tenascin-C
- Extracellular matrix
- Mouse model
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine