Pressure overload-induced right ventricular failure is associated with re-expression of myocardial tenascin-C and elevated plasma tenascin-C levels
M Hessel, P Steendijk, B den Adel, C Schutte… - Cellular Physiology and …, 2009 - karger.com
M Hessel, P Steendijk, B den Adel, C Schutte, A van der Laarse
Cellular Physiology and Biochemistry, 2009•karger.comAbstract Background: We investigated whether (1) monocrotaline (MCT)-induced right
ventricular (RV) dilatation is associated with re-expression of myocardial tenascin-C
(TNC),(2) elevated plasma TNC levels can be used as a marker of ventricular dilatation, and
(3) MCT-induced RV dilatation is associated with alterations of other remodeling-related
proteins. Methods: Rats were treated with MCT in low dose (30 mg/kg, MCT30, n= 10) to
induce compensated RV hypertrophy, in high dose (80 mg/kg, MCT80, n= 11) to induce RV …
ventricular (RV) dilatation is associated with re-expression of myocardial tenascin-C
(TNC),(2) elevated plasma TNC levels can be used as a marker of ventricular dilatation, and
(3) MCT-induced RV dilatation is associated with alterations of other remodeling-related
proteins. Methods: Rats were treated with MCT in low dose (30 mg/kg, MCT30, n= 10) to
induce compensated RV hypertrophy, in high dose (80 mg/kg, MCT80, n= 11) to induce RV …
Abstract
Background: We investigated whether (1) monocrotaline(MCT)-induced right ventricular (RV) dilatation is associated with re-expression of myocardial tenascin-C (TNC), (2) elevated plasma TNC levels can be used as a marker of ventricular dilatation, and (3) MCT-induced RV dilatation is associated with alterations of other remodeling-related proteins. Methods: Rats were treated with MCT in low dose (30 mg/kg, MCT30, n=10) to induce compensated RV hypertrophy, in high dose (80 mg/kg, MCT80, n=11) to induce RV failure, and with saline as control (CONT, n=9). After 4 weeks, RV function was assessed. TNC gene expression, protein levels, and plasma levels were assayed. Myocardial gene expression of integrin subunit α6 and β1, and myocardial proMMP2 and proMMP9 levels were assessed. Results: TNC gene expression in the RV of MCT80 rats was significantly upregulated compared with RV of CONT (4-fold, p<0.001) and MCT30 rats (3-fold, p<0.01), whereas TNC gene expression was very low in LV and IVS of MCT80 rats, and absent in those of CONT and MCT30 rats. Myocardial TNC protein levels were only observed in MCT80 rats, and were higher in RV (0.62±0.64 ng/mg) than in LV (0.21±0.44 ng/mg) or IVS (0.21±0.09 ng/mg) (p<0.01, RV vs LV and IVS). Plasma levels of TNC were significantly elevated in MCT80 rats compared with CONT (p<0.05). RV volumes correlated positively with TNC plasma levels and RV ejection fraction correlated negatively with TNC plasma levels. MCT-induced RV failure was also associated with a significant downregulation of integrin α6 gene expression (by 48%, p<0.01). Conclusions: MCT-induced RV failure is associated with an upregulation of TNC gene expression, resulting in re-expression of myocardial TNC protein levels, and elevated TNC plasma levels. As RV ejection fraction correlated significantly with TNC plasma levels, TNC plasma levels may serve as a marker of ventricular failure. De-adhesive properties of TNC in combination with a downregulation of integrin α6 may have caused cardiomyocyte slippage, leading to adverse ventricular remodeling.
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