title: Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction.
abstract: BACKGROUND
  Transforming growth factor (TGF)-beta is a locally generated cytokine involved in healing processes and tissue fibrosis, all relevant for cardiac remodeling and the development of heart failure after myocardial infarction (MI). However, data regarding the function of TGF-beta after ischemic injury are inconclusive.
  
  
  RESULTS
  We tested the effect of TGF-beta inhibition by application of a blocking antibody in mice with MI. Starting 1 week before or 5 days after coronary artery ligation mice were treated with intraperitoneal injections of an anti-TGF-beta (5 mg/kg bodyweight 1D11, Genzyme) or control antibody. Mortality over 8 weeks was significantly higher in the groups treated with the anti-TGF-beta antibody. Both, pre or post MI treatments were associated with increased left ventricular dilatation after MI as determined by serial echocardiography. In anti-TGF-beta treated mice collagen production decreased and matrix-metalloproteinase expression increased. However, the expression of TGF pro-inflammatory cytokine TNF-alpha was not altered by the treatment. Anti-TGF-beta treatment before or after coronary artery ligation increases mortality and worsens left ventricular remodeling in mice with non-reperfused MI. The detrimental effects of TGF-beta inhibition may be mediated by alterations in extracellular matrix remodeling.
authors.affiliation: Medizinische Klinik und Poliklinik I, Herz-/Kreislaufzentrum, Universitätsklinikum Würzburg, 97080, Würzburg, Germany. frantz_s@medizin.uni-wuerzburg.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Frantz
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Anna
authors.initials: A
authors.lastname: Adamek
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
authors.forename: Abed
authors.initials: A
authors.lastname: Sallam
authors.forename: Sebastian K G
authors.initials: SK
authors.lastname: Maier
authors.forename: Scott
authors.initials: S
authors.lastname: Lonning
authors.forename: Hong
authors.initials: H
authors.lastname: Ling
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D004452:Echocardiography; D004562:Electrocardiography; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000401:mortality* / Q000473:pathology; D009205:Myocarditis / Q000000981:diagnostic imaging / Q000401:mortality* / Q000473:pathology; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000401:mortality* / Q000473:pathology; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D016212:Transforming Growth Factor beta; D003094:Collagen