The regulation of angiogenesis by hypoxia is an important component of homeostatic mechanisms that link vascular oxygen supply to metabolic demand. Molecular characterization of angiogenic pathways, identification of hypoxia-inducible factor (HIF) as a key transcriptional regulator of these molecules, and the definition of the HIF hydoxylases as a family of dioxygenases that regulate HIF in accordance with oxygen availability have provided new insights into this process. Here we review these findings, and the role of HIF in developmental, adaptive and neoplastic angiogenesis. We also discuss the implications of oncogenic activation of extensive, physiologically interconnected hypoxia pathways for the tumor phenotype.

Original publication

DOI

10.1038/nm0603-677

Type

Journal article

Journal

Nat Med

Publication Date

06/2003

Volume

9

Pages

677 - 684

Keywords

Animals, DNA-Binding Proteins, Gene Expression Regulation, Developmental, Humans, Hydroxylation, Hypoxia, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Neoplasms, Neovascularization, Pathologic, Neovascularization, Physiologic, Nuclear Proteins, Protein Isoforms, Protein Subunits, Transcription Factors