Tenascin‐C aggravates ventricular dilatation and angiotensin‐converting enzyme activity after myocardial infarction in mice

Abstract

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.

Keywords

• Tenascin‐C
• Heart failure
• Myocardial infarction
• Isolated working heart
• Mouse model
• Extracellular matrix