Impact of exogenous VEGF administration after subtotal liver resection

Aims: Recent data suggest that vascular endothelial growth factor (VEGF) can improve liver regeneration after partial hepatectomy. It is unclear, whether exogenous administration of VEGF can also be used to ameliorate impaired liver regeneration and improve overall survival after massive (90%) resection of the liver.

Methods: To determine the effect of exogenous and endogenous VEGF after partial hepatectomy (PH), rats were subjected to 90% PH and treated with either VEGF, anti-VEGF or NaCl. Postoperatively (3h –4weeks) liver body weight ratio (LBR), hepatocyte proliferation (Ki-67) and biochemical markers (AST, ALT, GLDH, bilirubin) were assessed. To further elucidate the underlying molecular mechanisms hepatic gene expression was determined by customized cDNA arrays and quantitative rt-PCR.

Results: VEGF did not enhance hepatic proliferation compared to NaCl or anti-VEGF-treated rats. Even though VEGF treated rats showed an increased LBR as well as reduced serum parameters, this did not reach statistical significance. The overall survival after 90% PH reached 65%, but did not differ significantly compared to NaCl or anti-VEGF treated animals (53% and 54%, respectively). Gene expression analysis showed a modulation of anti-apoptotic and cell cycle control genes independent from VEGF.

Conclusions: Our data suggest that, in contrast to partial hepatectomy, VEGF does not play a significant role after subtotal hepatectomy in the rat model. This may be due to the fact that the mechanisms responsible for liver regeneration differ between these models.