title: Intrahepatic expression and release of vascular endothelial growth factor following orthotopic liver transplantation in the rat.
abstract: BACKGROUND
  Morphological and functional changes to sinusoidal endothelial cells mediated by soluble factors released from activated Kupffer cells, including cytokines, are considered pivotal events in ischemia/reperfusion injury (IRI) to liver grafts. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific cytokine with potent pro-inflammatory and mitogenic effects. We investigated the possible role of VEGF in IRI to liver grafts using a syngeneic rat orthotopic liver transplantation model.
  
  
  METHODS
  Transplantation was performed in Lewis rats using livers preserved for various periods of time (24-48 hr) in University of Wisconsin solution at 4 degrees C. Systemic VEGF levels were measured by enzyme-linked immunosorbent assay (ELISA). Intrahepatic VEGF expression was analyzed by Northern blotting and in situ hybridization. The effects of anti-VEGF neutralizing antibody treatment on the extent of IRI were assessed by measuring liver function tests, lipid peroxidation, and metalloproteinase activity.
  
  
  CONCLUSIONS
  VEGF is expressed and released in a biphasic pattern during the early postoperative period after liver transplantation. Anti-VEGF antibody treatment, administered during reperfusion, decreased the degree of damage, suggesting that VEGF may have a role in IRI to liver grafts.
authors.affiliation: The Recanati/Miller Transplant Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. Peter.Boros@MSSM.EDU
authors.forename: P
authors.initials: P
authors.lastname: Boros
authors.forename: A
authors.initials: A
authors.lastname: Tarcsafalvi
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Megyesi
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: C M
authors.initials: CM
authors.lastname: Miller
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D015342:DNA Probes / Q000235:genetics; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism; D016031:Liver Transplantation / Q000502:physiology*; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009500:Neutralization Tests; D009926:Organ Preservation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000235:genetics / Q000503:physiopathology; D014185:Transplantation, Isogeneic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D000911:Antibodies, Monoclonal; D015342:DNA Probes; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020778:Matrix Metalloproteinase 2