Ang-1 and Ang-2 are involved in cell-cell and cell-matrix binding [139, [144] [145] [146] . Endothelial permeability is greatly dependent on cell-cell adhesion. The major adherens junction is largely composed of vascular-endothelial cadherin. This complex can be disrupted by VEGF, leading to increased vascular permeability [147, 148] , which can be antagonized by Ang-1 [149, 150] . ECs can also bind to the matrix through the binding of Ang-1 to integrins, which can mediate some of the effects of Ang-1 without Tie2 phosphorylation [146, 151] . At low Ang-1 concentrations, integrin and Tie2 can cooperate to stabilize ECs [151] . Ang-2 might play a role in inflammatory diseases such as vasculitis by disrupting the cell-cell junction and inducing denudation of the basal membrane [152] . Ang-1 can mediate the translocation of Tie2 to endothelial cell-cell contacts and induce Tie2-Tie2 bridges with signal pathway activation, leading to diminished paracellular permeability [65] .