Antiangiogenic response after 70% hepatectomy and its relationship with hepatic regeneration and angiogenesis in rats

Surgery. 2010 Feb;147(2):288-94. doi: 10.1016/j.surg.2009.10.015. Epub 2009 Dec 11.

Abstract

Background: The aim of this study was to evaluate the antiangiogenic response and its relation to regeneration and angiogenesis after 70% hepatectomy in a rat model.

Methods: Sixty-four Wistar albino rats were included in the study. Animals were allocated into 8 groups (n = 8). After a 70% hepatectomy, liver regeneration, angiogenesis, and antiangiogenic response were evaluated in the remnant liver on days 0, 1, 2, 3, 5, 7, 10, and 14. Regeneration and angiogenesis were determined with immunoreactivity to proliferating cell nuclear antigen and vascular endothelial growth factor. Antiangiogenic response was evaluated by detecting collagen 18 m RNA with reverse transcriptase polymerase chain reaction.

Results: We showed that liver regeneration peaked at day 1, whereas angiogenesis in the periportal and perisinusoidal areas reached their peak values on days 3 and 7, respectively. Both regeneration and angiogenic activity around perisinusoidal hepatocytes returned to basal activity on the day 10. Antiangiogenic response first appeared on day 5, reached a peak on day 10, and returned to basal values on day 14.

Conclusion: Collagen18 mRNA expression is present in the normal liver during the regenerative process. We suggest that the stimulus that causes the cessation of regeneration process may come from hepatocytes, and collagen 18 produced by hepatocytes may modulate this event by inhibiting the angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / metabolism
  • Animals
  • Collagen Type XVIII / metabolism
  • Female
  • Hepatectomy*
  • Hepatocytes / metabolism
  • Liver / blood supply*
  • Liver Regeneration / physiology*
  • Neovascularization, Physiologic*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Collagen Type XVIII
  • Proliferating Cell Nuclear Antigen
  • Vascular Endothelial Growth Factor A