Molecular Signatures of Obstructive Sleep Apnea in Adults: A Review and Perspective

被引:235
作者
Arnardottir, Ema S. [1 ,2 ,3 ]
Mackiewicz, Miroslaw [2 ]
Gislason, Thorarinn [1 ,3 ]
Teff, Karen L. [4 ,5 ]
Pack, Allan I. [2 ,3 ]
机构
[1] Landspitali Univ Hosp, Dept Resp Med & Sleep, IS-108 Reykjavik, Iceland
[2] Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, Div Sleep Med,Dept Med, Philadelphia, PA 19104 USA
[3] Univ Iceland, Fac Med, Reykjavik, Iceland
[4] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA
[5] Univ Penn, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA
关键词
Obstructive sleep apnea; molecular mechanisms; chronic intermittent hypoxia; sleep fragmentation; pathophysiology; POSITIVE AIRWAY PRESSURE; CHRONIC INTERMITTENT HYPOXIA; TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; FACTOR-KAPPA-B; ANGIOTENSIN-CONVERTING ENZYME; ATRIAL-NATRIURETIC-PEPTIDE; ENDOPLASMIC-RETICULUM STRESS; SYMPATHETIC-NERVOUS-SYSTEM; MESSENGER-RNA EXPRESSION;
D O I
10.1093/sleep/32.4.447
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The consequences of obstructive sleep apnea (OSA) are largely mediated by chronic intermittent hypoxia and sleep fragmentation. The primary molecular domains affected are sympathetic activity, oxidative stress and inflammation. Other affected domains include adipokines, adhesion molecules and molecules that respond to endoplasmic reticulum stress. Changes in molecular domains affected by OSA, assessed in blood and/or urine, can provide a molecular signature for OSA that could potentially be used diagnostically and to predict who is likely to develop different OSA-related comorbidities. High-throughput discovery strategies such as microarrays, assessing changes in gene expression in circulating blood cells, have the potential to find new candidates and pathways thereby expanding the molecular signatures for OSA. More research is needed to fully understand the pathophysiological Significance of these molecular signatures and their relationship with OSA comorbidities. Many OSA subjects are obese, and obesity is an independent risk factor for many comorbidities associated with OSA. Moreover, obesity affects the same molecular pathways as OSA. Thus, a challenge to establishing a molecular signature for OSA is to separate the effects of OSA from obesity. We propose that the optimal strategy is to evaluate the temporal changes in relevant molecular pathways during sleep and, in particular, the alterations from before to after sleep when assessed in blood and/or urine. Such changes will be at least partly a consequence of chronic intermittent hypoxia and sleep fragmentation that occurs during sleep.
引用
收藏
页码:447 / 470
页数:24
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