title: Targeting the ROS-HIF-1-endothelin axis as a therapeutic approach for the treatment of obstructive sleep apnea-related cardiovascular complications.
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.
authors: Université Grenoble Alpes, Laboratoire HP2, Grenoble F-38042, France; INSERM U1042, Grenoble F-38042, France.
authors: Elise
authors: E
authors: Belaidi
authors: Université Grenoble Alpes, Laboratoire HP2, Grenoble F-38042, France; INSERM U1042, Grenoble F-38042, France.
authors: Jessica
authors: J
authors: Morand
authors: Université Grenoble Alpes, Laboratoire HP2, Grenoble F-38042, France; INSERM U1042, Grenoble F-38042, France.
authors: Emmanuelle
authors: E
authors: Gras
authors: Université Grenoble Alpes, Laboratoire HP2, Grenoble F-38042, France; INSERM U1042, Grenoble F-38042, France; CHU de Grenoble, Grenoble F-38042, France.
authors: Jean-Louis
authors: JL
authors: Pépin
authors: Université Grenoble Alpes, Laboratoire HP2, Grenoble F-38042, France; INSERM U1042, Grenoble F-38042, France. Electronic address: diane.ribuot@univ-grenoble-alpes.fr.
authors: Diane
authors: D
authors: Godin-Ribuot
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000150:complications; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors; D012720:Severity of Illness Index; D015398:Signal Transduction; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000503:physiopathology / Q000628:therapy
chemical_list: D019332:Endothelin-1; D051793:Hypoxia-Inducible Factor 1; D017382:Reactive Oxygen Species
keywords: Cardiovascular disease; Endothelin-1; Hypoxia inducible factor-1; Intermittent hypoxia; Obstructive sleep apnea; Oxidative stress