Journal
JOURNAL OF APPLIED PHYSIOLOGY
Volume 88, Issue 4, Pages 1474-1480Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jappl.2000.88.4.1474
Keywords
angiogenesis; glycolysis; ischemia; pulmonary hypertension; vascular endothelial growth factor; hypoxia-inducible factor 1
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Funding
- NHLBI NIH HHS [R01-HL-55338] Funding Source: Medline
- NIDDK NIH HHS [R01-DK-39869] Funding Source: Medline
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All organisms can sense O-2 concentration and respond to hypoxia with adaptive changes in gene expression. The large body size of mammals necessitates the development of multiple complex physiological systems to ensure adequate O-2 delivery to all cells under normal conditions. The transcriptional regulator hypoxia-inducible factor 1 (HIF-1) is an essential mediator of O-2 homeostasis. HIF-1 is required for the establishment of key physiological systems during development and their subsequent utilization in fetal and postnatal life. HIF-1 also appears to play a key role in the pathophysiology of cancer, cardiovascular disease, and chronic lung disease, which represent the major causes of mortality among industrialized societies. Genetic or pharmacological modulation of HIF-1 activity in vivo may represent a novel therapeutic approach to these disorders.
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