Effects of the neural and inflammatory response to stress on cerebrovascular risk in HIV infection

应激后的神经和炎症反应对 HIV 感染脑血管风险的影响

• 批准号: 10224349
• 负责人: Felicia C. Chow
• 金额: $ 20.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224349
• 关键词: Accounting; Address; Age; Aging; Amygdaloid structure; Area; Atherosclerosis; Award; Blood Vessels; Brain; Brain imaging; Cardiometabolic Disease; Cardiovascular Diseases; Cerebrovascular Disorders; Cerebrum; Chronic; Clinical Research; Clinical Trials; Data; Dementia; Development; Diagnosis; Disease; Endothelium; Environment; Evolution; Face; Feasibility Studies; Funding; Future; General Population; Goals; HIV; HIV Infections; Health; Hypertension; Individual; Inflammation; Inflammatory; Inflammatory Response; Infrastructure; Interleukin-1 beta; Interleukin-6; Intervention; Ischemic Stroke; Knowledge; Laboratories; Link; Measurement; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Neurologic; Neurology; Observational Study; Participant; Pathogenesis; Pathway interactions; Patient Recruitments; Play; Population; Positron-Emission Tomography; Psychological Stress; Public Health; Randomized Controlled Trials; Research; Research Infrastructure; Research Personnel; Risk; Risk Marker; Risk Reduction; Role; Smoking; Stress; Stroke; Structure; Techniques; Training; Transcranial Doppler Ultrasonography; United States National Institutes of Health; Viral reservoir; antiretroviral therapy; cardiovascular risk factor; career development; cerebrovascular; cerebrovascular health; clinical trial analysis; cost effective; cytokine; design; effectiveness testing; endothelial dysfunction; fluorodeoxyglucose positron emission tomography; immune activation; improved; inhibitor/antagonist; insight; mindfulness; mindfulness intervention; mindfulness-based stress reduction; monocyte; multimodality; novel; patient oriented; perceived stress; post intervention; preservation; prevent; primary outcome; relating to nervous system; research and development; skills; stress reduction; stroke event; stroke risk; treatment as usual; vascular risk factor

PROJECT SUMMARY This is an application for a K23 award for Dr. Felicia Chow, who is establishing herself as an investigator in patient-oriented clinical research at the intersection of HIV and cerebrovascular disease. This K23 award will provide Dr. Chow with the support necessary to develop new research skills and attain practical and conceptual expertise in 4 key areas: 1) brain and vascular FDG-PET imaging, 2) mechanisms and measurement of psychological stress, 3) advanced statistical techniques for observational data, and 4) design, conduct and analysis of clinical trials. Dr. Chow has assembled an interdisciplinary team of mentors (Dr. Priscilla Hsue, an expert in the role of inflammation and endothelial dysfunction in the pathogenesis of cardiovascular disease in HIV; Dr. Gil Rabinovici, an expert in use of multimodal brain imaging, including novel brain PET techniques, to improve diagnosis of dementia; Dr. Elissa Epel, an expert on measurement of stress and its effects on inflammation and cardiometabolic disease; Dr. Frederick Hecht, an expert on stress and mindfulness-based interventions in HIV; Dr. Peter Bacchetti, an expert on statistical approaches to analyzing observational HIV data), who will guide her research and career development. This multi-layered mentorship structure, embedded in a highly collaborative training environment, will be critical to her development into an independent investigator, with the ultimate goal of optimizing cerebrovascular health in people living with HIV. With the evolution of HIV infection into a chronic, treatable disease, people with HIV face excess risk of several non-AIDS-related complications, including stroke. Traditional vascular risk factors (e.g., hypertension, smoking) account for only a portion of excess cerebrovascular risk in HIV. This proposal will investigate the role of psychological stress, which is highly prevalent in people with HIV, in HIV-associated cerebrovascular risk. Dr. Chow hypothesizes that psychological stress activates pro-inflammatory pathways that contribute to elevated cerebrovascular risk in HIV. She will leverage the research infrastructure of two NIH-funded studies to evaluate the association of stress with the neural inflammatory pathway (i.e., amygdala activity, immune activation, inflammatory cytokines) in Aim 1 and with cerebrovascular risk markers (i.e., carotid arterial inflammation on FDG-PET and cerebral vasoreactivity by transcranial Doppler ultrasound) in Aim 2 in a cross-section of people with well-controlled HIV. In Aim 3, she will pilot a controlled trial of a mindfulness-based stress reduction intervention in a subset of high-stress individuals with HIV to gain preliminary insight into the impact of mindfulness on the neural inflammatory pathway and on cerebrovascular risk markers. This proposal is a crucial step toward uncovering the contribution of psychological stress to cerebrovascular risk in people with HIV and developing a larger randomized controlled trial to rigorously test the effectiveness of a stress reduction intervention as an adjunctive strategy to improving cerebrovascular health in people with HIV, which will be the focus of an R01 application to be prepared and submitted before the end of the award period.

项目总结