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

Dogrul, Ahmet Bulent; Colakoglu, Tamer; Kosemehmetoglu, Kemal; Birben, Esra; Yaman, Elif; Gedikoglu, Gokhan; Abbasoglu, Osman

doi:10.1016/j.surg.2009.10.015

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Volume 147, Issue 2 , Pages 288-294, February 2010

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

Ahmet Bulent Dogrul, MD
- Department of General Surgery, Medical School, Hacettepe University, Ankara, Turkey
- Reprint requests: Ahmet Bulent Dogrul, MD, Hacetepe Universitesi Tıp Fakültesi, Genel Cerrahi AD 06100, Sıhhiye/Ankara, Turkey.
Tamer Colakoglu, MD
- Department of General Surgery, Medical School, Hacettepe University, Ankara, Turkey
Kemal Kosemehmetoglu, MD
- Department of Pathology, Medical School, Hacettepe University, Ankara, Turkey
Esra Birben
- Pediatric Allergy and Asthma Research Laboratory, Medical School, Hacettepe University, Ankara, Turkey
Elif Yaman
- Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey
Gokhan Gedikoglu
- Department of Pathology, Medical School, Hacettepe University, Ankara, Turkey
Osman Abbasoglu, MD
- Department of General Surgery, Medical School, Hacettepe University, Ankara, Turkey

Accepted 5 October 2009. published online 11 December 2009.

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.