Endothelial Plasticity: Shifting Phenotypes through Force Feedback

Figure 4

Disturbed shear stress and high cyclic strain signaling in endothelial-mesenchymal transition. Disturbed shear stress induces EndMT through several mechanisms. Disturbed shear stress activates latent TGFβ by liberating it from LAP, after which TGFβ can induce Smad2/3 signaling. Disturbed shear stress induces the expression of BMP4 which causes ROS formation and the activity of NFκB. Lastly, disturbed shear stress induces NOX and XO activity resulting in the generation of ROS. All these signaling intermediates culminate in EndMT. Increased cyclic strain (>10%) induces the FAK-dependent activation of Rho-kinases. Rho activity causes the translocation of VE-Cadherin from the cell membrane into cytoplasmic vesicles and causes a reduction in endothelial cell-cell contacts. Cyclic strain-dependent Wnt-β-catenin activity induces EndMT in part by the induction of Snail and Slug and the further activation of Rho activity.