title: Roles of vascular endothelial growth factor and endothelial nitric oxide synthase during revascularization and regeneration after partial hepatectomy in a rat model.
abstract: OBJECTIVE
  Angiogenesis is an essential process in liver regeneration. Nitric oxide (NO) and vascular endothelial growth factor (VEGF) are the main regulators of normal and pathological angiogenesis. This study aimed to determine the roles of NO derived from endothelial nitric oxide synthase (eNOS) and VEGF in sinusoidal endothelial cell (SEC) proliferation during liver regeneration.
  
  
  METHODS
  Sprague-Dawley rats underwent a 70% partial hepatectomy (PHx), and were euthanized 0, 24, 48, 72, or 168 h later. Liver regeneration and SEC proliferation were evaluated. The protein expression of VEGF and eNOS was examined by a Western blot analysis. The rats were also treated with the NO synthase inhibitor N (G)-nitro-L-arginine-methyl ester (L-NAME) to examine its effects on liver regeneration and SEC proliferation.
  
  
  RESULTS
  The proliferating cell nuclear antigen (PCNA) labeling index of hepatocytes was significantly increased at 24 h after PHx. The eNOS protein expression and NO production were significantly increased from 72 to 168 h. The expression of VEGF protein was significantly increased at 72 h. L-NAME significantly inhibited the increases in the liver mass and decreased the PCNA labeling index of hepatocytes at 24 h. L-NAME also inhibited the induction of VEGF protein at 72 h.
  
  
  CONCLUSIONS
  Endothelial NOS and VEGF coordinately regulate SEC proliferation during liver regeneration. Sinusoidal endothelial cell proliferation is necessary and is an important step in liver regeneration.
authors.affiliation: Department of Disaster and Emergency Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshida
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Akahoshi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kawanaka
authors.forename: Shohei
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Nao
authors.initials: N
authors.lastname: Kinjo
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.forename: Morimasa
authors.initials: M
authors.lastname: Tomikawa
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashizume
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D042783:Endothelial Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000166:cytology; D008115:Liver Regeneration; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester