Hypoxia-inducible factors and obstructive sleep apnea.
J Clin Invest
; 130(10): 5042-5051, 2020 10 01.
Article
in En
| MEDLINE
| ID: mdl-32730232
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sleep Apnea, Obstructive
/
Basic Helix-Loop-Helix Transcription Factors
/
Hypoxia-Inducible Factor 1
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Clin Invest
Year:
2020
Document type:
Article