MACS/WIHS Combined Cohort Study: Cook County Clinical Research Site (CC_CRS) - OAR Sleep Supplement

MACS/WIHS 联合队列研究：库克县临床研究中心 (CC_CRS) - OAR 睡眠补充剂

• 批准号: 10658775
• 负责人: Mardge H Cohen
• 金额: $ 70.01万
• 依托单位: HEKTOEN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658775
• 关键词: Address; Aging; Anti-Inflammatory Agents; Atherosclerosis; Biological Process; Cardiometabolic Disease; Catabolism; Catecholamines; Chronic; Circadian Dysregulation; Cohort Studies; Complex; County; Data; Data Store; Disease; Enzymes; Essential Amino Acids; Extrahepatic; Foundations; Funding; Goals; HIV; HIV therapy; High Prevalence; Hormones; Human body; Hydrocortisone; Individual; Inflammation; Inflammatory; Infrastructure; Interferons; Interleukin-6; Intervention; Kynurenine; Length; Link; Measures; Mediating; Melatonin; Molecular; Moods; National Heart, Lung, and Blood Institute; Neurotransmitters; Participant; Pathway interactions; Peripheral; Persons; Plasma; Play; Process; Property; Quality of life; Reporting; Research Personnel; Research Priority; Risk; Sampling; Serotonin; Sleep; Sleep disturbances; Stress; TNF gene; Testing; Tryptophan; Tryptophan 2,3 Dioxygenase; Tryptophanase; Viral; Viral Proteins; Woman; Wrist; actigraphy; antiretroviral therapy; biological sex; cardiometabolic risk; cardiometabolism; circadian; clinical research site; cohort; comorbidity; cooking; cytokine; depressive symptoms; disorder risk; early onset; immune activation; insight; men; multidisciplinary; neurotoxic; novel; poor sleep; sex; sleep quality

ABSTRACT The objective of this supplement application is to investigate targeted kynurenine (KYN) pathway metabolites as molecular mechanisms by which objectively measured habitual sleep and circadian disruption increase risk for HIV-associated cardiometabolic disease and to determine whether these relationships differ by biological sex and HIV disease status. We will measure targeted KYN pathway metabolites in stored plasma (n=800) from well characterized MACS/WIHS Combined Cohort Study (MWCCS) men who already have habitual sleep measures collected, validated, and systematically scored via one week continuous wrist actigraphy (Philips Respironics Actiwatch Spectrum Plus). There will be no MWCCS participant and field staff burden for this supplement. No study to date has examined KYN pathway activation as a mechanism linking sleep and circadian disruption to HIV-related and inflammatory mediated comorbidities such as cardiometabolic disease in a mixed sex sample nor has this been accomplished with representation across all HIV disease status groups (well and poorly controlled HIV with comparison to uninfected controls). Results will provide novel insights into biological sex and HIV disease status differences in the mechanistic relationships between sleep and circadian disruption, KYN pathway activation, and HIV-associated cardiometabolic disease and provide a strong foundation upon which to test targeted sleep and circadian interventions to reduce risk for HIV- associated comorbidities in men and women aging with HIV.

摘要 本补充申请的目的是研究靶向犬尿氨酸（KYN）途径代谢物 由于客观测量的习惯性睡眠和昼夜节律紊乱的分子机制增加了风险， HIV相关的心脏代谢疾病，并确定这些关系是否因生物学 性和艾滋病毒疾病状况。我们将测量储存血浆中的靶向KYN途径代谢物（n=800） 来自已习惯性睡眠的MACS/WIHS联合队列研究（MWCCS）男性 通过一周的连续腕关节活动记录仪（Philips）收集、验证和系统评分的测量结果 Respironics Actiwatch Spectrum Plus）。这不会给MWCCS参与者和现场工作人员带来负担 补充.到目前为止，还没有研究将KYN通路激活作为连接睡眠和睡眠的机制。 对HIV相关和炎症介导的合并症（如心脏代谢疾病）的昼夜节律破坏 在混合性别样本中，也没有在所有艾滋病毒疾病状态中实现这一点 组（与未感染对照组相比，HIV控制良好和不良）。结果将提供新的 深入了解生物性别和艾滋病毒疾病状态的差异，在睡眠之间的机械关系 和昼夜节律破坏，KYN通路激活，以及HIV相关的心脏代谢疾病，并提供了一个 在此基础上测试有针对性的睡眠和昼夜节律干预措施，以降低艾滋病毒的风险- 与HIV感染的男性和女性老年人相关的合并症。