Gene

Obstructive sleep apnea

Cell biology

Biology

Baroreflex

Reactive oxygen species

Endocrinology

Cardiology

Biochemistry

Hypoxia (environmental)

Heart rate

Organic chemistry

Blood pressure

Oxygen

Insulin resistance

Sleep apnea

Oxidative stress

Apnea

Intermittent hypoxia

Internal medicine

Transcription factor

Medicine

Chemistry

Hypoxia-inducible factors

Diabetes mellitus

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