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Pharmacol Ther. 2016 Dec;168:1-11. doi: 10.1016/j.pharmthera.2016.07.010. Epub 2016 Aug 2.

Targeting the ROS-HIF-1-endothelin axis as a therapeutic approach for the treatment of obstructive sleep apnea-related cardiovascular complications.

Author information

1
Université Grenoble Alpes, Laboratoire HP2, Grenoble F-38042, France; INSERM U1042, Grenoble F-38042, France.
2
Université Grenoble Alpes, Laboratoire HP2, Grenoble F-38042, France; INSERM U1042, Grenoble F-38042, France; CHU de Grenoble, Grenoble F-38042, France.
3
Université Grenoble Alpes, Laboratoire HP2, Grenoble F-38042, France; INSERM U1042, Grenoble F-38042, France. Electronic address: diane.ribuot@univ-grenoble-alpes.fr.

Abstract

Obstructive sleep apnea (OSA) is now recognized as an independent and important risk factor for cardiovascular diseases such as hypertension, coronary heart disease, heart failure and stroke. Clinical and experimental data have confirmed that intermittent hypoxia is a major contributor to these deleterious consequences. The repetitive occurrence of hypoxia-reoxygenation sequences generates significant amounts of free radicals, particularly in moderate to severe OSA patients. Moreover, in addition to hypoxia, reactive oxygen species (ROS) are potential inducers of the hypoxia inducible transcription factor-1 (HIF-1) that promotes the transcription of numerous adaptive genes some of which being deleterious for the cardiovascular system, such as the endothelin-1 gene. This review will focus on the involvement of the ROS-HIF-1-endothelin signaling pathway in OSA and intermittent hypoxia and discuss current and potential therapeutic approaches targeting this pathway to treat or prevent cardiovascular disease in moderate to severe OSA patients.

KEYWORDS:

Cardiovascular disease; Endothelin-1; Hypoxia inducible factor-1; Intermittent hypoxia; Obstructive sleep apnea; Oxidative stress

PMID:
27492897
PMCID:
PMC5643507
DOI:
10.1016/j.pharmthera.2016.07.010
[Indexed for MEDLINE]
Free PMC Article

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