The Ang/Tie system is an integrated, highly complex system of checks and balances ( Figure 1) [45,54]. The response of ECs to Ang-1 and Ang-2 depends on the location of the cells and the biological and biomechanical context [97, 98] . It is believed that PI3K/Akt is among the most important downstream signalling pathways and that VEGF is one of the most important modulators of effects. Below we describe in more detail how this system responds to changes in homeostatic balances under various conditions of damage and repair.