title: The Protective Effects of Bevacizumab in Bleomycin-Induced Experimental Scleroderma.
abstract: BACKGROUND
  The capillary networks are less dense and have irregular structures in scleroderma. These abnormalities result in lower capillary blood flow causing severe tissue hypoxia, which is a major stimulus for angiogenesis. However, current knowledge about compensatory angiogenesis is ambiguous in scleroderma. Bevacizumab is an inhibitor of vascular endothelial growth factor (VEGF).
  
  
  OBJECTIVE
  The aim of the present study is to evaluate the protective effects of bevacizumab in bleomycin (BLM)- -induced dermal fibrosis.
  
  
  METHODS
  This study involved 4 groups of Balb/c mice (n = 10 per group). Mice in the control group received 100 μL/day of phosphate-buffered saline (PBS) subcutaneously, while the other 3 groups were given 100 μg/day of BLM (dissolved in 100 μL PBS) subcutaneously, for 4 weeks. Mice in BLM-treated 3rd and 4th groups also received bevacizumab (1 or 5 mg/kg twice a week, intraperitoneally). At the end of the fourth week, all mice were sacrificed and blood and tissue samples were obtained.
  
  
  RESULTS
  The BLM applications increased the dermal thicknesses, tissue hydroxyproline contents, and α-smooth muscle actin-positive (α-SMA+) cell counts, and led to histopathologically prominent dermal fibrosis. The bevacizumab treatments decreased the tissue hydroxyproline contents and dermal thicknesses, and these improvements were more prominent at doses by which α-SMA+ cell counts were markedly decreased, in the BLM-injected mice.
  
  
  CONCLUSIONS
  In our study, inhibition of VEGF with bevacizumab treatments prevented the BLM-induced dermal fibrosis suggesting that VEGF expression contributes to the pathogenesis of scleroderma.
authors.affiliation: Department of Rheumatology, Faculty of Medicine, Firat University, Turkey.
authors.forename: Suleyman S
authors.initials: SS
authors.lastname: Koca
authors.affiliation: Department of Rheumatology, Faculty of Medicine, Ondokuz Mayis University, Turkey.
authors.forename: Metin
authors.initials: M
authors.lastname: Ozgen
authors.affiliation: Department of Pathology, Faculty of Medicine, Firat University, Turkey.
authors.forename: Adile F
authors.initials: AF
authors.lastname: Dagli
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Firat University, Turkey.
authors.forename: Nevzat
authors.initials: N
authors.lastname: Gozel
authors.affiliation: Department of Pathology, Faculty of Medicine, Firat University, Turkey.
authors.forename: Ibrahim H
authors.initials: IH
authors.lastname: Ozercan
authors.affiliation: Department of Rheumatology, Faculty of Medicine, Firat University, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Isik
mesh_terms: D000199:Actins / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000068258:Bevacizumab / Q000494:pharmacology*; D001761:Bleomycin; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005355:Fibrosis; D006909:Hydroxyproline / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000199:Actins; D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; C544013:alpha-smooth muscle actin, mouse; C467480:vascular endothelial growth factor A, mouse; D001761:Bleomycin; D000068258:Bevacizumab; D006909:Hydroxyproline
keywords: VEGF; bevacizumab; dermal fibrosis; scleroderma