Figure 1.

Schematic representation of post-ischaemic neovascularisation. (1a) Under normoxic conditions, DLL4-Notch-1 signalling is balanced in ECs. (1b) Under normoxic conditions, small collateral arterioles may connect main arteries. (2a) Low O₂ conditions increase HIF-1a levels, which in turn stimulates the expression of VEGF-A (represented as small blue dots). In response to VEGF-A, Dll4 expression increases on the surface of tip cells (purple cell). Dll4 receptors on tip cells bind to Notch receptors on the surface of stalk cells (yellow cells) activating Dll4/Notch signalling pathway. Dll4—Notch-1 signalling directs ECs into migrating tip or proliferating stalk cells. In response to VEGF-A, VEGFR expression increases on the filopodia of tip cells (represented as protrusions on the tip cell), which then migrate towards VEGF-A with the stalk cells proliferating behind them. This results in the expansion of the vessel lumen and the formation of sprouts on the vessel wall (angiogenesis). (2b) When a coronary artery is occluded due to the formation of plaque within the arterial wall, there is increased shear stress in the collateral arterioles. In response to shear stress, collateral arteriole diameter increases in size (arteriogenesis).