Molecular signatures of obstructive sleep apnea

该项目的总体目标是解决以下假设： 阻塞性睡眠呼吸暂停（OSA）是一种常见的睡眠障碍，是睡眠期间相关生物标志物的变化。 在睡眠呼吸暂停中，事件导致睡眠片段化和周期性脱氧/复氧。拟 通过评估血液中的生物标志物，可以检测到这些变化将导致分子后果。 为了确定哪些变化是由于阻塞性睡眠呼吸暂停引起的，哪些是由于昼夜节律/睡眠机制引起的，将进行研究。 在CPAP有效治疗前后的OSA患者中，以及在类似内脏器官损害的对照中， 将在睡眠前、睡眠中和睡眠后对生物标志物进行多项评估。 由于提出了这些动态变化的幅度在睡眠期间将受到影响， 在伴有心血管合并症的OSA受试者中， 在4组受试者中进行：有和没有这些疾病的瘦和肥胖。在评估生物标志物时， 主要结果变量为：尿异前列腺素（氧化应激）;血浆TNF α（炎症）; 血浆去甲肾上腺素（交感神经激活）;和游离脂肪酸。次要生物标志物为：IL-6， 尿去甲肾上腺素;尿去甲肾上腺素;血糖、ICAM、瘦素。以补充对 循环生物标志物，将使用利用细胞窗口的方法。将分离单核细胞 从每一个血液样本（之前，期间和之后的睡眠）和RNA提取。关键基因的表达 通过RT-PCR和微阵列研究进行评估，将在一个受试者子集中进行，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调查之间的差异 有或无心血管合并症的OSA患者。将评估三个方面：a） 患有合并症的个体是否有更多的氧化应激和炎症变化， B）患有合并症的个体是否具有 较低水平的保护机制褪黑激素（睡眠期间分泌的抗氧化剂），IL-10（抗氧化剂）， 炎症）; c）基于使用最近开发的 CV SNP阵列。最后，数据将用于确定是否有诊断性尿液和/或血液检查 关于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.