HIF-1: mediator of physiological and pathophysiological responses to hypoxia

Abstract

All organisms can sense O2concentration 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 O2delivery to all cells under normal conditions. The transcriptional regulator hypoxia-inducible factor 1 (HIF-1) is an essential mediator of O2homeostasis. 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.