title: Pressure overload-induced right ventricular failure is associated with re-expression of myocardial tenascin-C and elevated plasma tenascin-C levels.
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 alpha6 and beta1, 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 alpha6 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 alpha6 may have caused cardiomyocyte slippage, leading to adverse ventricular remodeling.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Marleen
authors.initials: M
authors.lastname: Hessel
authors.forename: Paul
authors.initials: P
authors.lastname: Steendijk
authors.forename: Brigit
authors.initials: B
authors.lastname: den Adel
authors.forename: Cindy
authors.initials: C
authors.lastname: Schutte
authors.forename: Arnoud
authors.initials: A
authors.lastname: van der Laarse
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism; D006352:Heart Ventricles / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016686:Monocrotaline; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019063:Tenascin / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D018497:Ventricular Dysfunction, Right / Q000139:chemically induced / Q000503:physiopathology*; D016278:Ventricular Function, Right / Q000502:physiology; D017725:Ventricular Pressure; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D016023:Integrins; D019063:Tenascin; D016686:Monocrotaline; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9