Vascular endothelial growth factor (VEGF) and VEGF receptor expression in biopsy samples of liver from dogs with congenital portosystemic shunts

J Comp Pathol. 2012 Jul;147(1):55-61. doi: 10.1016/j.jcpa.2011.09.001. Epub 2011 Oct 11.

Abstract

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased liver mass, development of intrahepatic portal vasculature and improved liver function. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The aim of this study was to investigate the role of VEGF and its receptor in the hepatic response to CPSS surgery. The study included 99 dogs with CPSS treated with either partial or complete suture attenuation. Forty-four dogs with partial attenuation underwent a second surgery for complete attenuation. The expression of VEGF and VEGF receptor 2 (VEGFR2) in biopsy samples of liver was assessed by immunohistochemistry with rabbit anti-human VEGF polyclonal antibody and mouse anti-human VEGFR2 monoclonal antibody. Expression of these molecules was graded. The proportion of samples expressing VEGF was significantly greater in samples from dogs with CPSS compared with control samples (P=0.04) and the proportion of samples expressing VEGFR2 was significantly greater in control samples compared with samples from dogs with CPSS (P=0.04). VEGF labelling grade decreased significantly (P=0.038) and VEGFR2 increased significantly (P=0.046) between first and second surgery. The decrease in VEGF may reflect transient expression, preferential expression of other factors, reperfusion of existing vessels and/or increased angiogenesis before surgery in the form of arterialization and subsequent reduction due to improved portal blood flow. Partial suture attenuation was associated with a degree of 'normalization' of VEGF and VEGFR2 expression when compared with the control samples. Further investigation is needed to provide more information on the hepatic response to CPSS surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Dog Diseases / congenital
  • Dog Diseases / pathology*
  • Dog Diseases / surgery
  • Dogs
  • Immunohistochemistry / veterinary
  • Liver / blood supply
  • Liver / metabolism
  • Liver / pathology*
  • Liver Diseases / congenital
  • Liver Diseases / metabolism
  • Liver Diseases / pathology*
  • Liver Diseases / surgery
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / veterinary*
  • Portal System / abnormalities*
  • Portal System / surgery
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Biomarkers
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2