The schematic representation shows the established endothelial-centric model of Ang/Tie signalling (left) and the revised bi-directional, reciprocal EC-pericyte model of vascular Tie2 signalling as derived from the findings of this study (right; red routes show newly identified pathways). Vascular Ang/Tie2 signalling has so far exclusively been related to Tie2 expression by EC. Ang1 acts paracrine and is secreted by pericytes and other cells. Ang2 is almost exclusively expressed by EC and thereby acts as dynamic autocrine modulator of Ang1/Tie2 signalling. Extending this model, the findings of this study demonstrate that functional Tie2 receptors are also expressed by pericytes. Consequently, Ang1 expressed by pericytes (and likely other cells) activates pericyte Tie2 and contributes thereby to vascular maturation. Ang2 is produced by EC and acts paracrine on pericytes, thereby contributing to vascular destabilization through direct pericyte effects.