Hypoxia induces the formation of hypoxia-inducible factor (HIF), which stimulates the release of vascular endothelial growth factor (VEGF).
In normal cells, this is regulated by Von Hippel-Lindau (VHL) protein which causes ubiquitination and degeneration of HIF1a.
Decrease in VHL protein increases levels of HIF1 which triggers angiogenic factors, including VEGF and PDGF which in turn leads to unregulated blood vessel growth.
