|M.Sc Student||Shushy-Eitan Moran|
|Subject||The Role of the Adherens Junctions (VE-cadherin, b-catenin)|
in Shear Stress Signal Transduction into Vascular
|Department||Department of Medicine||Supervisor||Ms. Nitzan Resnick|
As blood flows through the arteries, it imparts physical forces (consisting of hydrostatic pressure, cyclic strain and shear stress) to the vascular wall that regulate a number of important physiological and pathological responses in blood vessels. Several in-vitro studies suggest that shear stress modulates endothelial structure and function, including rapid changes in protein structure, gene expression and cytoskeleton reorganization. These raise the questions of how are mechanical forces transduced by endothelial cells into a biological response, and is there a “shear stress receptor”. This study shows that shear stress induces a very rapid change in the cellular localization of the VEGF receptor 2 the adherens junction molecules
VE-cadherin and b-catenin in vascular endothelial cells. These changes are accompanied by the formation of a multi-member complex containing the VEGF receptor 2/VE-cadherin /b-catenin, a complex recently shown to play a major role in neovascularization. In endothelial cells lacking VE-cadherin (VE cadherin -/-) shear stress mediated phosphorylation of Akt1 and the stress kinase p38, as well as transcription mediated by Shear Stress Response Element (SSRE), do not occur. These results suggest for the first time that VEGF receptor 2 and the adherens junction act as shear stress co-receptors and suggest a mechanism through which shear stress augment new blood vessel formation.