VEGF can act as vascular permeability factor in the hepatic sinusoids through upregulation of porosity of endothelial cells

VEGF is shown to be a vascular permeability factor (VPF) as well as a growt h stimulatory factor on endothelial cells. In the hepatic sinusoids, endoth elial cells express flt-1 and KDR/flk-1, receptors for VEGF. These cells, i n primary culture, proliferate in response to VEGF stimulation. However, th e role of VEGF as VPF in the hepatic sinusoids is to be elucidated. The eff ect of VEGF on the porosity of sinusoidal endothelial cells was studied. Si nusoidal endothelial cells were isolated from rats and cultured in DMEM con taining 10% FCS on plastic dishes coated with type I collagen for 16 and 48 h for morphological examination and cell-number measurement, respectively. When the cells were cultured without VEGFF addition, their number was decr eased at 48 h compared to that at 16 h. However, the number was unchanged i n the cells cultured with VEGF at 10 ng/mL and increased with addition of V EGF at 100 ng/mL. Scanning electron microscopic examination revealed that s ieve-plate appearance of the cells was impaired in culture with no VEGF add ition, but the appearance was maintained in culture with VEGF at 10 ng/mL o r more. The cells cultured with VEGF at 100 ng/mL showed significantly incr eased number and size of pores compared to the cells cultured with VEGF at 10 ng/mL, suggesting that sinusoidal endothelial cells proliferating in res ponse to VEGF may increase their porosity. It is concluded that VEGF can ac t as VPF in the hepatic sinusoids through regulation of endothelial cell po rosity. (C) 2001 Academic Press.