Tenascin-C aggravates ventricular dilatation and angiotensin-converting enzyme activity after myocardial infarction in mice.
ESC Heart Fail
; 7(5): 2113-2122, 2020 10.
Article
in En
| MEDLINE
| ID: mdl-32639674
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 ANDRESULTS:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tenascin
/
Myocardial Infarction
Limits:
Animals
Language:
En
Journal:
ESC Heart Fail
Year:
2020
Document type:
Article
Affiliation country:
Austria