Intrahepatic expression and release of vascular endothelial growth factor following orthotopic liver transplantation in the rat

Transplantation. 2001 Sep 15;72(5):805-11. doi: 10.1097/00007890-200109150-00011.


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.

Results/conclusion: 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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Base Sequence
  • DNA Probes / genetics
  • Endothelial Growth Factors / antagonists & inhibitors
  • Endothelial Growth Factors / genetics*
  • Endothelial Growth Factors / metabolism*
  • Gene Expression
  • In Situ Hybridization
  • Liver / metabolism
  • Liver Transplantation / physiology*
  • Lymphokines / antagonists & inhibitors
  • Lymphokines / genetics*
  • Lymphokines / metabolism*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Neutralization Tests
  • Organ Preservation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Lew
  • Reperfusion Injury / genetics
  • Reperfusion Injury / physiopathology
  • Transplantation, Isogeneic
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Antibodies, Monoclonal
  • DNA Probes
  • Endothelial Growth Factors
  • Lymphokines
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Matrix Metalloproteinase 2