Molecular signatures of obstructive sleep apnea

这个项目的总体目标是解决这样的假设，即最优的分子签名 常见的阻塞性睡眠呼吸暂停(OSA)是指睡眠期间相关生物标志物的变化。 在睡眠呼吸暂停中，事件会导致睡眠碎裂和周期性的脱氧/复氧。有建议说 这些变化将导致分子后果，可以通过评估血液中的生物标记物来检测。 为了确定哪些变化是由于阻塞性睡眠呼吸暂停综合症引起的，哪些是由于昼夜节律/睡眠机制引起的，将进行研究 阻塞性睡眠呼吸暂停患者CPAP有效治疗前后及相似脏器对照 没有OSA的肥胖。将在睡眠前、期间和之后对生物标记物进行多种评估。 由于提出了这些动态变化在睡眠期间的大小将受到影响 根据内脏肥胖的程度，并在患有心血管并发症的阻塞性睡眠呼吸暂停综合症患者中更严重，研究将 受试者分为4组：瘦的和肥胖的，有或没有这样的病症。在评估生物标志物方面 主要结果变量将是：尿异前列腺素(氧化应激)；血浆肿瘤坏死因子(炎症)； 血浆去甲肾上腺素(交感神经激活)；和游离脂肪酸。二级生物标志物将是：IL-6， 尿去甲肾上腺素；尿去甲肾上腺素；葡萄糖、细胞间黏附分子、瘦素。以补充对 循环生物标记物，将使用一种利用细胞窗口的方法。 从每个血样(睡前、睡中和睡后)提取RNA。关键基因的表达将是 通过RT-PCR和微阵列研究将在一部分受试者中进行，以评估 所有基因的表达作为OSA的结果。一个特别的重点将是研究 患有和不伴有心血管并发症的阻塞性睡眠呼吸暂停患者。 合并症患者是否有更多的氧化应激和炎性变化 OSA的程度比没有这种并存的人要高；b)有并存的人是否有 较低水平的保护机制：冶炼甲素(一种在睡眠中分泌的抗氧化剂)、IL-10(抗氧化剂 炎症性)；c)不同的基因变体，基于使用最近开发的 CV SNP数组。最后，数据将被用来确定是否有诊断性尿液和/或血液测试 为了OSA。

The overall goal of this project is to address the postulate that the optimal molecular signature for the common disorder obstructive sleep apnea (OSA) is change in relevant biomarkers during the sleep period. In sleep apnea, events lead to sleep fragmentation and cyclical deoxygenation/reoxygenation. It is proposed that these changes will lead to molecular consequences can be detected by assessing biomarkers in blood. To determine which changes are due to OSA and which to circadian/sleep mechanisms, studies will be done in patients with OSA before and after effective treatment with CPAP and also in controls of similar visceral adiposity without OSA.Multiple assessments of biomarkers will be made before, during and after sleep. Since it is proposed that the magnitude of these dynamic changes across the sleep period will be affected by degree of visceral obesity and be greater in OSA subjects with cardiovascular comorbidities, studies will be done in 4 groups of subjects: lean and obese with and without such morbidities. In assessing biomarkers the primary outcome variables will be: urinary isoprostanes (oxidative stress); plasma TNFa (inflammation); plasma norepinephrine (sympathetic activation); and free fatty acids. Secondary biomarkers will be: IL-6, urinary norepinephrine; urinary normetanephrine; glucose, ICAM, leptin. To complement assessment of circulating biomarkers, an approach utilizing a cellular window will be used. Monocytes will be separated from each blood sample (before, during and after sleep) and RNA extracted. Expression of key genes will be assessed by RT-PCR and microarray studies will be performed in a subset of subjects to assess changes in expression of all genes as a resuft of OSA.A particular focus will be investigating differences between individuals with OSA with and without cardiovascular comorbidities. Three aspects will be evaluated: a) whether individuals with comorbidities have more oxidative stress and inflammatory change for equivalent degrees of OSA than individuals without such comorbidities; b) whether individuals with comorbidities have lower levels of protective mechanismsmelatonin (an anti-oxidant secreted during sleep), IL-10 (anti- inflammatory); c) different gene variants based on a genetic association study using a recently developed CV SNP array. Finally, data will be used to determine whether there is a diagnostic urine and/or blood test for OSA.