Vascular endothelial growth factor attenuates hepatic sinusoidal capillarization in thioacetamide-induced cirrhotic rats

AIM: To investigate the effect of vascular endothelial growth factor (VEGF) transfection on hepatic sinusoidal capillarization. METHODS: Enhanced green fluorescent protein (EGFP)/VEGF transfection was confirmed by immunofluorescence microscopy and immunohistoche-mistry both in primary hepatocytes and in normal liver. Cirrhotic rats were generated by thioacetamide (TAA) administration and then divided into a treatment group, which received injections of 400 mu g of plasmid DNA encoding an EGFP-VEGF fusion protein, and a blank group, which received an equal amount of normal saline through the portal vein. The portal vein pressure was measured in the normal and cirrhotic state, in treated and blank groups. The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy (TEM), while the relative abundance of VEGF transcripts was examined by Gene array. RESULTS: Green fluorescent protein was observed in the cytoplasms of liver cells under immunofluorescence microscopy 24 h after transfection with EGFP/VEGF plasmid in vitro. Staining with polyclonal antibodies against VEGF illustrated that hepatocytes expressed were significant differences in the number of fenestrae and portal vein pressures between normal and cirrhotic rats (7.40 +/- 1.71 vs 2.30 +/- 1.16 and 9.32 +/- 0.85 cmH(2)O vs 17.92 +/- 0.90 cmH(2)O, P < 0.01), between cirrhotic and treated rats (2.30 +/- 1.16 cmH(2)O vs 4.60 +/- 1.65 and 17.92 +/- 0.90 cmH(2)O vs 15.52 +/- 0.93 cmH(2)O, P < 0.05) and between the treatment group and the blank group (4.60 +/- 1.65 cmH(2)O vs 2.10 +/- 1.10 cmH(2)O and 15.52 +/- 0.93 cmH(2)O vs 17.26 +/- 1.80 cmH(2)O, P < 0.05). Gene-array analysis revealed that the relative abundance of transcripts of VEGF family members decreased in the cirrhotic state and increased after transfection. CONCLUSION: Injection of a plasmid encoding VEGF through the portal vein is an effective method to induce the formation of fenestrae and decrease portal vein pressure in cirrhotic rats. Therefore, it may be a good choice for treating hepatic cirrhosis and portal hypertension. (c) 2008 WJG. All rights reserved.