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 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.

The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding–Debanding of the Ascending Aorta

“…We have recently highlighted the role of TN-C in regulating interstitial fibrosis and myocardial function in response to pressure overload, demonstrating that high levels of TN-C were associated with adverse LV remodeling [ 10 ]. In addition, our recent study demonstrated that TN-C upregulation was associated with angiotensin-converting enzyme-1 (ACE-1) activity enhancement, suggesting the molecular interaction between ACE-1 and TN-C [ 11 ]. However, knowledge on the impact of TN-C on the ECM changes associated with reverse remodeling and cardiac function still remains elusive.…”

Involvement of the Extracellular Matrix Proteins Periostin and Tenascin C in Nasal Polyp Remodeling by Regulating the Expression of MMPs

“…There is substantial evidence that tenascin C contributes to tissue remodeling via the upregulation of MMP-9 in the mouse model of the cardiovascular system (e.g., cardiac remodeling, hepatic ischemia/reperfusion, subarachnoid hemorrhage, etc.). [15,24,28,29] and tenascin C is capable of inducing the expression of MMP-9 in breast cancer cells and isolated neutrophils. [24,30] Recently, Kanagala et al [31] found higher levels of plasma MMP-8 in heart failure patients with tenascin C above the median plasma concentration than in those with tenascin C below the median plasma concentration.…”

“…Tenascin C, as an ECM protein, could be increased in parallel with MMPs in some pathological states. [15] However, the regulatory role of tenascin C on MMPs in nasal polyps remains unknown. In the present study, we found that tenascin C induced the expression of MMP-3, MMP-8, and MMP-9 in the nasal epithelium, but not in broblasts.…”

“…[7,10] However, whether the two ECM proteins contribute to the formation of CRSwNP via tissue remodeling is unknown. Given that the levels of MMPs in NP tissues are elevated, [5,11,12] and there is evidence supporting the association between the two ECM proteins (periostin and tenascin C) and the expression of MMPs beyond nasal mucosa [13][14][15]. We hypothesized that periostin and tenascin C might have an impact on the expression of MMPs in NPs.…”

The Roles of Tenascins in Cardiovascular, Inflammatory, and Heritable Connective Tissue Diseases

“…TNC is reported to be involved in a variety of cardiovascular diseases (83,93,94). In the pathogenesis of myocardial damage and cardiac dysfunction, animal experiments have demonstrated that TNC is involved in adverse remodeling of myocardium due to myocardial infarction (95,96) and myocarditis (97). TNC has been reported to promote myocardial hypertrophy, fibrosis (98,99) and cardiac dysfunction (100) in animal models of cardiac hypertrophy and myocardial infarction.…”