Involvement of Hypoxia-Inducible Factor 1 in Physiological and Pathological Responses to Continuous and Intermittent Hypoxia: Role of Reactive Oxygen Species

The hypoxia-inducible factors (HIFs) are transcriptional activators that mediate homeostatic responses to hypoxia. At the cellular level, HIF-1 mediates adaptive metabolic responses to hypoxia that serve to maintain energy and redox homeostasis by reducing mitochondrial generation of reactive oxygen species (ROS). At the systemic level, HIFs control erythropoiesis and thereby maintain blood O2-carrying capacity and delivery of O2 to body tissues. In contrast to these adaptive responses, patients with obstructive sleep apnea are subjected to chronic intermittent hypoxia, a nonphysiological stimulus that induces HIF-1, which mediates a maladaptive response, systemic hypertension.