M.Sc Thesis

M.Sc StudentShleper Maria
SubjectThe Effect of Hemodynamic Forces on Liver Endothelial Cell
Morphology and Gene Expression
DepartmentDepartment of Medicine
Supervisor ASSOCIATE PROF. Gad Spira


Following 70% partial hepatectomy in rats, blood flow-to-liver mass ratio increases reaching maximal values 24 hours post surgery. These alterations are associated with the formation of fused fenestrae (gaps) as early as 10’, increasing in subsequent time points and abating by 10 days. During the same timeframe, the lumen of the sinusoids contract and many platelets adhered to the lining endothelial.

Isolated liver endothelial cells subjected to 10 dynes/cm2 for 15’ were examined by real time RT-PCR and immunofluorescence for abundance and localization of VEGF and angiopoetins receptors. Following shear stress a shift from low cytoplasmic to abundant nuclear localization of VEGFR2 was evident. A similar behavior was presented by neuropilin 1. VEGFR-1 nuclear staining and neuropilin 2 perinuclear localization were not affected by shear stress.  Real time PCR analysis of the above receptors indicated a significant increase in VEGFR1, VEGFR2 and neuropilin1 mRNA. No change was observed for neuropilin 2. Immunofluorescent studies revealed a rapid (5’) binding of VEGFR-2 to VE-cadherin. A complex comprising VE-cadherin - b-catenin was also evident at 5’ post shear stress. 15 minutes exposure to shear stress was associated with a complex of VE-cadherin and b-catenin, but not of VE-cadherin and VEGFR-2. These rapid and transient changes of VEGFR-2 and adhesion proteins point to the complexity of this potential mechanoreceptor. Our data indicate a possible role for hemodynamic forces in the early events of liver regeneration.