Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice

Gastroenterology. 2004 Mar;126(3):886-94. doi: 10.1053/j.gastro.2003.12.012.


Background & aims: Portal hypertension is a frequent syndrome that develops in patients with chronic liver diseases, which are one of the most common causes of death in adults worldwide. The most serious clinical consequences of portal hypertension are related to the development of portal-systemic collateral vessels. Those include hepatic encephalopathy and massive bleeding from ruptured gastroesophageal varices. The high relevance of these collateral vessels prompted us to investigate the mechanism underlying its formation in a murine model of portal hypertension.

Methods: To determine whether the development of portal-systemic collateral vessels in portal hypertension is a vascular endothelial growth factor (VEGF)-dependent angiogenic process, we assessed the effects of a monoclonal antibody against VEGF receptor-2 on the formation of these collateral vessels in mice with portal hypertension induced by partial portal vein ligation. We also studied the effects of a selective and specific inhibitor of VEGF receptor-2 autophosphorylation in partial portal vein-ligated rats.

Results: A significant and marked inhibition in the formation of portal-systemic collateral vessels was observed in both partial portal vein-ligated mice and rats treated with anti-VEGF receptor-2 monoclonal antibodies or with the inhibitor of VEGF receptor-2 autophosphorylation, respectively, compared with animals receiving control solutions.

Conclusions: Our present study shows that formation of collateral vessels is an angiogenesis-dependent process that can be markedly inhibited by blockade of the VEGF signaling pathway. These findings will make angiogenesis a focal point of research in portal hypertension and may lead to novel approaches for therapy of patients with chronic liver diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Blood Vessels / pathology
  • Collateral Circulation / drug effects*
  • Hypertension, Portal / pathology
  • Hypertension, Portal / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / physiopathology*
  • Neovascularization, Pathologic / prevention & control
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Portal System / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / immunology*


  • Antibodies, Monoclonal
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2