Regulation of Angiogenesis and Blood Supply

Rapidly growing embryos, tumors, and wounded tissues deplete physiological oxygen levels. This leads to a state of hypoxia, which triggers angiogenesis—the formation of new blood vessels. 

Under hypoxic conditions, a transcription factor, hypoxia-inducible factor 1, or HIF-1, accumulates and induces the expression of vascular endothelial growth factor or VEGF and other angiogenic factors. 

VEGF diffuses through the extracellular matrix to reach nearby endothelial cells and stimulate them to differentiate into specialized tip cells. Tip cells start expressing the delta-like notch ligand four or DLL4.

DLL4 binds the Notch receptors of neighboring cells, signaling them to proliferate and differentiate into stalk cells.

The endothelial tip migrates following the VEGF gradient and reaches the hypoxic tissues.

As blood flows through these newly formed vessels, it delivers oxygen and growth nutrients to the rapidly growing or injured tissue.

Once the oxygen level increases, proteasomal enzymes degrade HIF1, stopping VEGF expression and inhibiting angiogenesis.