title: Myocardial connective tissue growth factor (CCN2/CTGF) attenuates left ventricular remodeling after myocardial infarction.
abstract: OBJECTIVE
  Myocardial CCN2/CTGF is induced in heart failure of various etiologies. However, its role in the pathophysiology of left ventricular (LV) remodeling after myocardial infarction (MI) remains unresolved. The current study explores the role of CTGF in infarct healing and LV remodeling in an animal model and in patients admitted for acute ST-elevation MI.
  
  
  RESULTS
  Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) and non-transgenic littermate controls (NLC) were subjected to permanent ligation of the left anterior descending coronary artery. Despite similar infarct size (area of infarction relative to area at risk) 24 hours after ligation of the coronary artery in Tg-CTGF and NLC mice, Tg-CTGF mice disclosed smaller area of scar tissue, smaller increase of cardiac hypertrophy, and less LV dilatation and deterioration of LV function 4 weeks after MI. Tg-CTGF mice also revealed substantially reduced mortality after MI. Remote/peri-infarct tissue of Tg-CTGF mice contained reduced numbers of leucocytes, macrophages, and cells undergoing apoptosis as compared with NLC mice. In a cohort of patients with acute ST-elevation MI (n = 42) admitted to hospital for percutaneous coronary intervention (PCI) serum-CTGF levels (s-CTGF) were monitored and related to infarct size and LV function assessed by cardiac MRI. Increase in s-CTGF levels after MI was associated with reduced infarct size and improved LV ejection fraction one year after MI, as well as attenuated levels of CRP and GDF-15.
  
  
  CONCLUSIONS
  Increased myocardial CTGF activities after MI are associated with attenuation of LV remodeling and improved LV function mediated by attenuation of inflammatory responses and inhibition of apoptosis.
authors.affiliation: Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Gravning
authors.forename: Stein
authors.initials: S
authors.lastname: Ørn
authors.forename: Ole Jørgen
authors.initials: OJ
authors.lastname: Kaasbøll
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Martinov
authors.forename: Cord
authors.initials: C
authors.lastname: Manhenke
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dickstein
authors.forename: Thor
authors.initials: T
authors.lastname: Edvardsen
authors.forename: Håvard
authors.initials: H
authors.lastname: Attramadal
authors.forename: Mohammed Shakil
authors.initials: MS
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology; D055513:Connective Tissue Growth Factor / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006333:Heart Failure / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D055436:Growth Differentiation Factor 15; D019394:Ki-67 Antigen; D055513:Connective Tissue Growth Factor; D002097:C-Reactive Protein; D019009:Proto-Oncogene Proteins c-kit