The main steps that endothelial cells take to form new blood vessels include: enzymatic degradation of capillary basement, endothelial cell proliferation, migration of endothelial cells, tubulogenesis, vessel fusion, pericyte stabilization and vessel pruning.
- In the early stages of angiogenesis (in response to VEGF induced by wounding and ischemia) the vascular basement is degraded by proteases.
- Following the disruption of the basement membrane, endothelial stalk cells then proliferate, migrate, and coalesce to form a lumen within a series of stalk cells.
- The stalk cells become the trunk of the newly formed capillary.
- Tubes must then be formed with lumens in order to carry out the flow of blood. This process is known as tubulogenesis.
- Next, when the tip cells of two or greater capillary sprouts come together at the source of VEGF-A secretion, the tip cells fuse together producing a continuous lumen in which oxygenated blood can flow through.
- When the tissues begin to receive adequate amounts of oxygen, VEGF-A levels return to near normal.
- The maturation and stabilization of the capillary requires pericytes and deposition of ECM along with shear stress and other signals.