Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis.
Inefficient vascular supply and the resultant reduction in tissue oxygen tension often lead to neovascularization in order to satisfy the needs of the tissue. Examples include the compensatory development of collateral blood vessels in ischaemic tissues that are otherwise quiescent for angiogenesis and angiogenesis associated with the healing of hypoxic wounds. But the presumptive hypoxia-induced angiogenic factors that mediate this feedback response have not been identified. Here we show that vascular endothelial growth factor (VEGF; also known as vascular permeability factor) probably functions as a hypoxia-inducible angiogenic factor. VEGF messenger RNA levels are dramatically increased within a few hours of exposing different cell cultures to hypoxia and return to background when normal oxygen supply is resumed. In situ analysis of tumour specimens undergoing neovascularization show that the production of VEGF is specifically induced in a subset of glioblastoma cells distinguished by their immediate proximity to necrotic foci (presumably hypoxic regions) and the clustering of capillaries alongside VEGF-producing cells.
D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology*; D002455:Cell Division; D015687:Cell Hypoxia; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology; D005909:Glioblastoma / Q000098:blood supply* / Q000473:pathology*; D006801:Humans; D008222:Lymphokines / Q000235:genetics* / Q000502:physiology*; D009336:Necrosis; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors