Figure 9. Proposed mechanism of VE‐PTP regulation of endothelial barrier function and atherogenesis in response to shear force.

In atheroprone regions of the aorta with disturbed flow and low average shear force (left), VE‐PTP‐Tie2 complexes in the plasma membrane promote Tie2 dephosphorylation, destabilization of intercellular junctions, increased permeability (small gaps between cells), and greater plasma leakage. Endothelial leakiness favors the development of atherosclerotic plaques under atherogenic conditions of lipid metabolism. By comparison, in atheroprotected regions, laminar flow with high average shear force (right) stimulates VE‐PTP (blue) redistribution to the downstream pole of endothelial cells, followed by internalization into endosomes. This change sequesters VE‐PTP from Tie2 (red), promotes Tie2 phosphorylation (yellow), stabilizes intercellular junctions, tightens the endothelial barrier, and reduces leakage. Inhibition of VE‐PTP drives the process from left to right, tightens the endothelial barrier, reduces leakage, and suppresses atherogenesis.