Research

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

Filip Braet¹ , Maria Shleper² , Melia Paizi² , Sergey Brodsky^3,4 , Natalia Kopeiko⁵ , Nitzan Resnick^2,6 and Gadi Spira²

¹  Molecular Cell Biology Unit, Department for Molecular Biomedical Research, Ghent University / VIB, Technologiepark 927, B-9052 Ghent, Belgium

²  Department of Anatomy and Cell Biology, The Bruce Rappaport Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion, Haifa 31096, Israel

³  Department of Physiology, The Bruce Rappaport Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion, Haifa 31096, Israel

⁴  Department of Medicine – Renal Research Institute, New York Medical College, Valhalla, NY 10595, USA

⁵  Department of Experimental Surgery, The Bruce Rappaport Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion, Haifa 31096, Israel

⁶  Vascular Research Center, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 11 Louis Pasteur Ave. NRB, Boston, MA 02115, USA

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Comparative Hepatology 2004, 3:7doi:10.1186/1476-5926-3-7

Published:	1 September 2004

Abstract

Background

Shear stress forces acting on liver sinusoidal endothelial cells following resection have been noted as a possible trigger in the early stages of hepatic regeneration. Thus, the morphology and gene expression of endothelial cells following partial hepatectomy or shear stress in vitro was studied.

Results

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.

Conclusion

Our data suggest a possible relation between elevated blood flow associated with partial hepatectomy and the early events occurring thereby.