Arnaud Claire, Dematteis Maurice, Pepin Jean-Louis, Baguet Jean-Philippe, Lévy Patrick
INSERM ERI17, Grenoble, 38043, France.
Semin Immunopathol. 2009 Jun;31(1):113-25. doi: 10.1007/s00281-009-0148-5. Epub 2009 Apr 29.
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.
阻塞性睡眠呼吸暂停（OSA）是一种高度流行的睡眠障碍，可导致心血管和代谢并发症。OSA也是一种多因素疾病，间歇性缺氧（IH）是相关心血管和代谢改变的主要触发因素。实际上，睡眠期间反复出现的咽部塌陷会导致缺氧-复氧的重复序列。这种IH会引发多种后果，如血流动力学、激素代谢、氧化和免疫炎症改变，这些改变可能相互作用并相互加重，导致动脉从适应性改变发展为退行性动脉粥样硬化重塑。在没有其他心血管危险因素的OSA患者中也发现了动脉粥样硬化，并且与夜间缺氧的严重程度有关。在OSA患者和实验性暴露于IH的啮齿动物中都已证实存在动脉改变的早期阶段，包括功能和结构变化。据报道，由于交感神经、内皮素和肾素-血管紧张素系统导致的血管反应性受损以及内皮功能障碍和/或血管收缩反应增加，也会导致血管重塑和炎症。氧化应激、炎症和血管重塑可由IH直接引发，并因OSA相关的激素代谢改变（如胰岛素抵抗、血脂异常和脂肪因子失衡）而进一步加重。正如在OSA患者和动物模型中所示，遗传易感性、合并症（肥胖）和生活习惯（高脂饮食）可能会加重动脉粥样硬化的发展或进展。其确切的分子机制在很大程度上仍然未知，对其的了解可能有助于确定预防策略的新靶点和/或开发OSA相关动脉粥样硬化的新治疗方法，尤其是在有心血管疾病风险的患者中。
