Transcriptional Regulation by Hypoxia-inducible Factor 1 Molecular Mechanisms of Oxygen Homeostasis

Human cells require O(2) for many metabolic processes, most notably oxidative phosphorylation, the major source of ATP generation, and hypoxia plays a significant pathophysiologic role in a variety of cardiovascular disorders. Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator of genes whose products, including erythropoietin, vascular endothelial growth factor, and glycolytic enzymes, are involved in systemic, local, and cellular responses to hypoxia that either increase O(2) delivery or induce alternative metabolic pathways that do not require O(2). The level of HIF-1 expression in cultured cells is proportional to the degree of hypoxia over the range of O(2) concentrations associated with physiologic and pathophysiologic conditions in vivo. Further investigation of HIF-1 function in vivo may lead to novel therapeutic approaches that modulate cellular responses to hypoxia/ischemia. (Trends Cardiovasc Med 1996;6:151-157).