Liver sinusoidal endothelial cell modulation upon resection and shear stress in vitro

Following partial hepatectomy blood flow-to-liver mass ratio reached maximal values 24 hrs post resection. Concomitantly, large fenestrae (gaps) were noted. Exposure of liver sinusoidal endothelial cells, in vitro, to physiological laminar shear stress forces was associated with translocation of vascular endothelial cell growth factor receptor-2 (VEGFR-2) and neuropilin-1 from perinuclear and faint cytoplasmic distribution to plasma membrane and cytoskeletal localization. Under these conditions, VEGFR-2 co-stains with VE-cadherin. Unlike VEGFR-2, the nuclear localization of VEGFR-1 was not affected by shear stress. Quantification of the above receptors showed a significant increase in VEGFR-1, VEGFR-2 and neuropilin-1 mRNA following shear stress.Our data suggest a possible relation between elevated blood flow associated with partial hepatectomy and the early events occurring thereby.Following partial hepatectomy (PHx) the remaining liver is transfused by normal blood volume, thereby exposing liver sinusoidal endothelial cells (LECs) to excess hemodynamic forces. These forces have been noted as an early event leading to liver restoration in rats [1-3]; however, the idea that quality of the blood rather than quantity has been the accepted dogma [4,5]. Based on time-scale events, shear stress inflicted on liver cells precedes the expression of factors some of which are expressed within minutes. Studies conducted in recent years indicate that shear stress induced NO leads to the expression of genes participating in liver regeneration including c-fos [6-8]. There is evidence demonstrating that increase of c-fos in PHx or portal branch ligation models is inhibited by N-nitro-L-arginine methyl ester, which blocks NO synthase [8]. The present study was undertaken to examine the molecular and ultrastructural effects of hemodynamic forces on LECs. We have chosen to focus on vascular endothelial cell growth factor (VEGF) receptors (VEGFRs), as these are present on endothelial