Hypoxia-inducible factor 1-alpha (HIF-1α) and Vascular endothelial growth factor A (VEGFA) (HIF-1α/VEGFA)

The Hypoxia-inducible factor 1-alpha (HIF-1α) and Vascular endothelial growth factor A (VEGFA) axis is a critical signaling pathway that mediates the cellular response to low oxygen levels. HIF-1α acts as a master transcription factor that stabilizes under hypoxic conditions and induces the expression of VEGFA, which subsequently promotes angiogenesis, vascular permeability, and cell survival (UniProt P41222, P15692). This axis is frequently overactivated in various cancers to support tumor growth and metastasis by ensuring an adequate blood supply (PubMed 12154373). It also plays a central role in the pathogenesis of neovascular eye diseases, such as age-related macular degeneration and diabetic retinopathy. Therapeutic strategies targeting this pathway include monoclonal antibodies like bevacizumab that neutralize VEGFA and emerging small molecules designed to inhibit HIF-1α activity. Clinical use of these inhibitors is often associated with safety concerns such as hypertension and impaired wound healing.

Other names

HIF1AVEGFVPFVascular permeability factorHypoxia-inducible factor 1 subunit alpha

Inhibition of the hypoxia-induced signaling cascade by either preventing the transcriptional activity of HIF-1α or neutralizing the downstream VEGFA ligand to suppress pathological angiogenesis.