Obstructive sleep apnea, immuno-inflammation, and atherosclerosis.
Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder leading to cardiovascular and metabolic complications. OSA is also a multicomponent disorder, with intermittent hypoxia (IH) as the main trigger for the associated cardiovascular and metabolic alterations. Indeed, recurrent pharyngeal collapses during sleep lead to repetitive sequences of hypoxia-reoxygenation. This IH induces several consequences such as hemodynamic, hormonometabolic, oxidative, and immuno-inflammatory alterations that may interact and aggravate each other, resulting in artery changes, from adaptive to degenerative atherosclerotic remodeling. Atherosclerosis has been found in OSA patients free of other cardiovascular risk factors and is related to the severity of nocturnal hypoxia. Early stages of artery alteration, including functional and structural changes, have been evidenced in both OSA patients and rodents experimentally exposed to IH. Impaired vasoreactivity with endothelial dysfunction and/or increased vasoconstrictive responses due to sympathetic, endothelin, and renin-angiotensin systems have been reported and also contribute to vascular remodeling and inflammation. Oxidative stress, inflammation, and vascular remodeling can be directly triggered by IH, further aggravated by the OSA-associated hormonometabolic alterations, such as insulin resistance, dyslipidemia, and adipokine imbalance. As shown in OSA patients and in the animal model, genetic susceptibility, comorbidities (obesity), and life habits (high fat diet) may aggravate atherosclerosis development or progression. The intimate molecular mechanisms are still largely unknown, and their understanding may contribute to delineate new targets for prevention strategies and/or development of new treatment of OSA-related atherosclerosis, especially in patients at risk for cardiovascular disease.
Arnaud
Claire
C
INSERM ERI17, Grenoble, 38043, France.
Dematteis
Maurice
M
Pepin
Jean-Louis
JL
Baguet
Jean-Philippe
JP
Lévy
Patrick
P
D054392:Adipokines / Q000097:blood / Q000276:immunology; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D050171:Dyslipidemias / Q000097:blood / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000235:genetics / Q000276:immunology; D007249:Inflammation; D007333:Insulin Resistance / Q000276:immunology; D010084:Oxidation-Reduction; D012084:Renin-Angiotensin System / Q000276:immunology; D020181:Sleep Apnea, Obstructive / Q000097:blood / Q000150:complications / Q000235:genetics / Q000276:immunology*; D014661:Vasoconstriction / Q000276:immunology
D054392:Adipokines