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DOI: 10.1055/s-0034-1367254
Tenascin-C enhances fibrosis and hypertrophy during pressure overload in the mouse heart
Introduction: The extracellular matrix protein Tenascin-C (TNC) influences cell adhesion and cardiac remodeling. It is primarily expressed after myocardial infarction (MI), but its role during ventricular hypertrophy remains completely unclear. Therefore, a minimal invasive mouse aortic banding model was established to investigate the influence of TNC during left ventricular pressure overload (PO).
Methods: Aortic banding was performed in TNC-knockout (TNC-KO) and wildtype (WT) mice: Following a partial sternotomy, a ligature was placed between the innominate and the left common carotid artery and tied around a 27-gauge needle to maintain equal knot tightness. Sham surgery was performed (TNC-KO-SHAM, WT-SHAM) respectively without tying the suture (n = 8 in every group). Histologic samples were collected after 1 week, 4 weeks, and 10 weeks. Also, hearts were assessed in vivo by cardiac magnetic resonance imaging after 10 weeks. Data are presented as mean ± SEM.
Results: Hemodynamic function was significantly decreased only in the WT banding group: ejection fraction (WT: 48.06 ± 4.48% vs. WT-SHAM: 62.20 ± 1.98%, p < 0.01; TNC-KO: 64.78 ± 3.87% vs. TNC-KO-SHAM: 72.03 ± 2.85%, n.s.), cardiac output (WT: 43.68 ± 4.23 ml/g vs. WT-SHAM: 82.80. ± 4.68 ml/g, p < 0.01; TNC-KO: 67.18 ± 7.45 ml/g vs. TNC-KO-SHAM: 83.94 ± 6.52 ml/g, n.s.). Also, septum thickness was significantly enlarged solely in operated WT mice (WT: 1.54 ± 0.09 mm vs. WT-SHAM: 1.11 ± 0.03 mm, p < 0.01; TNC-KO: 1.20 ± 0.03 mm vs, TNC-KO-SHAM: 1.04 ± 0.03 mm, n.s.). Histologic evaluation revealed increasing levels of fibrosis in the WT banding group over time but minimal fibrosis in the TNC-KO banding group.
Discussion: Hemodynamic function of TNC-null mice remained significantly less affected by ventricular remodeling during pressure overload. Also, there were only marginal signs of fibrosis in this group. It seems that TNC influences ventricular remodeling not only after MI but also during PO.