Hypoxia-inducible factors

Chemistry

Baroreflex

Oxygen

Biochemistry

Hypoxia (environmental)

Oxidative stress

Intermittent hypoxia

Reactive oxygen species

Organic chemistry

Blood pressure

Biology

Gene

Endocrinology

Obstructive sleep apnea

Cell biology

Insulin resistance

Sleep apnea

Internal medicine

Heart rate

Diabetes mellitus

Transcription factor

Medicine

Journal of Clinical Investigation

Intermittent hypoxia (IH) is a hallmark manifestation of obstructive sleep apnea (OSA), a widespread disorder of breathing. This Review focuses on the role of hypoxia-inducible factors (HIFs) in hypertension, type 2 diabetes (T2D), and cognitive decline in experimental models of IH patterned after O2 profiles seen in OSA. IH increases HIF-1α and decreases HIF-2α protein levels. Dysregulated HIFs increase reactive oxygen species (ROS) through HIF-1-dependent activation of pro-oxidant enzyme genes in addition to reduced transcription of antioxidant genes by HIF-2. ROS in turn activate chemoreflex and suppress baroreflex, thereby stimulating the sympathetic nervous system and causing hypertension. We also discuss how increased ROS generation by HIF-1 contributes to IH-induced insulin resistance and T2D as well as disrupted NMDA receptor signaling in the hippocampus, resulting in cognitive decline.

Hypoxia-inducible factors and obstructive sleep apnea