Endothelial Plasticity: Shifting Phenotypes through Force Feedback

Figure 2

Endothelial shear stress sensing. Endothelial cells sense LSS through a number of mechanisms. Shear stress sensing through the endothelial glycocalyx is mediated by the syndecans and glypicans, which activate PKC signaling. Luminal β1-integrins also anchor to the endothelial glycocalyx and activate focal adhesion kinase (FAK). The G-protein-coupled receptors of /Gα₁₁ sense shear stress and activate downstream PI3K and Ca²⁺ signaling. The junctional mechanosensory complex consisting of PECAM-1, VEGFR2, and VE-Cadherin mediates PI3K and MAPK (MEKK3) signaling. Signaling through these mechanosensors culminates in activation of Akt, PKA, AMPK, and MEK5/Erk5 which collectively maintain the endothelial phenotype.