Effect of vascular endothelial growth factor on hepatic regenerative activity following partial hepatectomy in rats

Background/Aims: Vascular endothelial growth factor (VEGF) is an angiogenic factor with a growth-promoting effect that is thought to be restricted to vascular endothelial cells, Its essential role during liver regeneration ha s yet to be determined. The aim of this study was to document the effect of exogenous VEGF administration on liver regeneration in rats undergoing sub maximal hepatic resections. Methods: Adult male Sprague-Dawley rats (n=4/group) undergoing 30% partial hepatectomy were administered 200 ng VEGF(165) intravenously and were sacri ficed at 24, 36, and 48 h postoperatively, Liver regeneration was monitored by measuring the restituted liver mass, proliferating cell nuclear antigen (PCNA) immunostaining, and hepatic PCNA protein by Western blot. Results: Changes in restituted liver mass 48 h postsurgery were more promin ent, but did not differ statistically between VEGF-treated and control rats (47% vs 29%; p<0.06). Nevertheless, PCNA immunostaining showed increased l abeling index of hepatocytes, apparent at 36 and 48 h after partial hepatec tomy (38% vs 18% [p<0.04] and 42% vs 11% [p<0.02], respectively). Hepatic P CNA proteins measured by Western blot showed a 3-fold increase in VEGF-trea ted rats 48 h postsurgery compared with controls (p<0.01). Conclusion: Exogenous VEGF administration early after partial hepatectomy s timulates liver regeneration in rats. Whether or not VEGF(165) is a direct mitogen for hepatocytes remains to be determined.