title: CCN2/CTGF attenuates myocardial hypertrophy and cardiac dysfunction upon chronic pressure-overload.
abstract: BACKGROUND
  Myocardial CCN2/CTGF (connective tissue growth factor) is strongly induced in heart failure (HF) and acts as a cardioprotective factor in ischemia/reperfusion injury. However, its functional role in myocardial hypertrophy remains unresolved.
  
  
  RESULTS
  Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) and non-transgenic littermate control (NLC) mice were subjected to chronic pressure-overload by abdominal aortic banding. After 4weeks of persistent pressure-overload, a time point at which compensatory hypertrophy of the left ventricle (LV) prevails, Tg-CTGF mice displayed diminished increase of LV mass compared with NLC. At study end-point after 12 weeks of sustained aortic constriction, the mice displayed LV dilatation and reduced cardiac function. Repeated transthoracic echocardiography during the 12 weeks of chronic pressure-overload, revealed attenuation of LV dilatation and virtually sustained systolic function in Tg-CTGF mice compared with NLC mice. Also, increase of LV mass was blunted in Tg-CTGF versus NLC mice at study end-point. Consistently, increases of myocardial ANP, BNP and skeletal α-actin mRNA levels were blunted in Tg-CTGF mice subjected to chronic pressure-overload. Furthermore, cardiac myocytes from Tg-CTGF mice displayed increased phospho-NFATc2 levels and attenuated hypertrophic response upon stimulation with α1-adrenoceptor agonist, indicating that CTGF attenuates hypertrophic signaling in cardiac myocytes. Increase of myocardial collagen contents in mice subjected to aortic banding was similar in Tg-CTGF and NLC mice, indicating that CTGF have minimal impact on myocardial collagen deposition.
  
  
  CONCLUSIONS
  This study provides novel evidence that CTGF attenuates cardiac hypertrophy upon chronic pressure-overload due to inhibition of signaling mechanisms that promote pathologic myocardial hypertrophy.
authors: Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and University of Oslo, Norway; Center for Heart Failure Research, University of Oslo, Norway.
authors: Jørgen
authors: J
authors: Gravning
authors: Mohammed Shakil
authors: MS
authors: Ahmed
authors: Thomas G
authors: TG
authors: von Lueder
authors: Thor
authors: T
authors: Edvardsen
authors: Håvard
authors: H
authors: Attramadal
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D004452:Echocardiography; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D017725:Ventricular Pressure
chemical_list: C526318:CCN2 protein, mouse; D055513:Connective Tissue Growth Factor; D012313:RNA
keywords: Aortic banding; CTGF; Cardiac hypertrophy; Heart failure; Transgenic mice