Hunyor Imre, Cook Kristina M
Department of Cardiology, Royal Prince Alfred Hospital , Sydney, New South Wales , Australia.
Faculty of Medicine and Health, University of Sydney School of Medicine , Sydney, New South Wales , Australia.
Am J Physiol Regul Integr Comp Physiol. 2018 Oct 1;315(4):R669-R687. doi: 10.1152/ajpregu.00036.2018. Epub 2018 Jul 11.
Obstructive sleep apnea (OSA) is common and linked to a variety of poor health outcomes. A key modulator of this disease is nocturnal intermittent hypoxia. There is striking epidemiological evidence that patients with OSA have higher rates of cancer and cancer mortality. Small-animal models demonstrate an important role for systemic intermittent hypoxia in tumor growth and metastasis, yet the underlying mechanisms are poorly understood. Emerging data indicate that intermittent hypoxia activates the hypoxic response and inflammatory pathways in a manner distinct from chronic hypoxia. However, there is significant heterogeneity in published methods for modeling hypoxic conditions, which are often lacking in physiological relevance. This is particularly important for studying key transcriptional mediators of the hypoxic and inflammatory responses such as hypoxia-inducible factor (HIF) and NF-κB. The relationship between HIF, the molecular clock, and circadian rhythm may also contribute to cancer risk in OSA. Building accurate in vitro models of intermittent hypoxia reflective of OSA is challenging but necessary to better elucidate underlying molecular pathways.
阻塞性睡眠呼吸暂停（OSA）很常见，且与多种不良健康后果相关。这种疾病的一个关键调节因素是夜间间歇性缺氧。有显著的流行病学证据表明，OSA患者的癌症发病率和癌症死亡率更高。小动物模型表明，全身性间歇性缺氧在肿瘤生长和转移中起重要作用，但其潜在机制尚不清楚。新出现的数据表明，间歇性缺氧以不同于慢性缺氧的方式激活缺氧反应和炎症途径。然而，在已发表的模拟缺氧条件的方法中存在显著的异质性，这些方法往往缺乏生理相关性。这对于研究缺氧和炎症反应的关键转录调节因子，如缺氧诱导因子（HIF）和核因子κB（NF-κB）尤为重要。HIF、分子时钟和昼夜节律之间的关系也可能导致OSA患者患癌症的风险增加。建立反映OSA的间歇性缺氧的准确体外模型具有挑战性，但对于更好地阐明潜在分子途径是必要的。
