Sleep as a novel pathway linking chronic psychological stress and inflammation

描述(申请人提供)：心血管疾病(CVD)是美国最主要的死亡原因，每年造成超过5000亿美元的经济负担。慢性应激被列为心血管疾病的主要生物行为风险因素之一，这种关系部分归因于应激期间炎症过程的加剧。一个令人兴奋的科学进步领域正在专注于确定慢性压力影响炎症活动的具体途径，越来越多的证据表明，睡眠可能是连接压力和炎症水平升高的一个关键机制。在压力时期，睡眠通常会被打乱。在预测炎症活动水平时，推进对压力和睡眠之间相互作用的理解是至关重要的，因为睡眠代表一种可改变的健康行为。也就是说，可以通过干预睡眠的方式来改善压力对炎症水平的有害影响，最终降低心血管疾病的风险。K08指导的临床科学家研究职业发展奖旨在以我之前的培训和研究为基础，调查睡眠作为连接慢性压力和与心血管疾病风险相关的炎症活动标记物的途径所起的作用。首先，这个奖项将提供一个机会，加深我对睡眠生理学、测量和研究方法的理解，并获得在纵向统计方法、妇女健康和基因表达/免疫生物学方面的高级培训。第二，作为一项正在进行的纵向研究的一部分，我将对长期应激和低压力的产妇照顾者进行为期18个月的跟踪调查，以检验睡眠和炎症测量之间的预期关联，包括循环炎症介质(IL-6、肿瘤坏死因子-α和C反应蛋白)和靶向炎症基因(IL-6、肿瘤坏死因子、白介素B)的单核细胞表达，以测试睡眠是否介导了压力-炎症联系。这项全面的培训计划和创新的研究研究将有助于阐明压力和睡眠之间的相互依赖关系，以预测对心血管健康至关重要的炎症过程。此外，这项研究的发现将为开发和应用针对睡眠行为的新治疗策略奠定基础，以降低患心血管疾病风险较高的个人，特别是那些经历高水平压力的人的炎症水平。

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is the foremost cause of mortality in the United States, and accounts for over $500 billion per year in economic burden. Chronic stress ranks as one of the leading biobehavioral risk factors for CVD, a relationship that is partially attributable to inflammatory processes elevated during stress. An exciting arena of scientific advancements is focusing on identifying the specific pathways through which chronic stress influences inflammatory activity with emerging evidence to suggest that sleep, which is commonly disrupted during periods of stress, may serve as one key mechanism linking stress and elevated levels of inflammation. It is critical to advance understanding of the interplay between stress and sleep in predicting levels of inflammatory activity because sleep represents a modifiable health behavior. That is, sleep can be targeted for intervention in ways that may ameliorate the deleterious effects of stress on levels of inflammation, and ultimately, CVD risk. This K08 Mentored Clinical Scientist Research Career Development Award seeks to build on my prior training and research to investigate the role of sleep as a pathway linking chronic stress and markers of inflammatory activity relevant to CVD risk. First, this award will provide the opportunity to deepen my understanding of sleep physiology, measurement, and research methodologies, as well as obtain advanced training in longitudinal statistical methods, women's health, and gene expression/immunobiology. Second, as part of an ongoing longitudinal study, I will examine the prospective associations between sleep, measured objectively using actigraphy, and measures of inflammation, including circulating inflammatory mediators (IL-6, TNF-alpha, and CRP) and monocyte expression of targeted inflammatory genes (IL6, TNF, IL1B) in chronically stressed and low stress maternal caregivers followed over 18-months to test whether sleep mediates the stress-inflammation link. This comprehensive training plan and innovative research study will help to elucidate the interdependent relationships between stress and sleep in predicting inflammatory processes key to cardiovascular health. Moreover, findings from this research will lay the foundation for the development and application of novel therapeutic strategies targeting sleep behavior to reduce levels of inflammation among individuals at elevated risk for CVD, particularly those experiencing high levels of stress.