Regulation of angiogenesis by hypoxia: role of the HIF system

CW Pugh, PJ Ratcliffe - Nature medicine, 2003 - nature.com
CW Pugh, PJ Ratcliffe
Nature medicine, 2003nature.com
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 …
Abstract
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.
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