Arsenic Metabolism, Menopause and Diabetes in the Strong Heart Study

强心研究中的砷代谢、更年期和糖尿病

• 批准号: 10331523
• 负责人: Cecile Delille Lahiri
• 金额: $ 22.05万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10331523
• 关键词: Age; Aging; Amenorrhea; Angiography; Animal Model; Antiviral Agents; Arsenic; Atherosclerosis; Biological; Biomedical Research; Biometry; Bone Density; Brain; CCL2 gene; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Cerebrovascular Disorders; Cessation of life; Chronic; Clinical Research; Communicable Diseases; Coronary; Development; Diabetes Mellitus; Disease; Environment; Estrogen Receptors; Estrogens; Exposure to; Extramural Activities; Female; Female of child bearing age; Fertility Rates; Fostering; Funding; Gender; Goals; HIV; HIV Infections; HIV Seronegativity; HIV antiretroviral; Health; Heart; Immune; Immune system; Immunologic Deficiency Syndromes; Immunology; Impairment; Inflammation; Inflammatory; Interdisciplinary Study; Interferon Type II; Interferons; Interleukin-1 beta; Interleukin-6; Ischemic Stroke; Leadership; Light; Magnetic Resonance Imaging; Matrix Metalloproteinases; Mediating; Menopause; Metabolism; Modeling; Musculoskeletal; Myocardial Infarction; NOS2A gene; Natural Killer Cells; Organ; Outcome; Ovarian; Participant; Pathogenesis; Pathology; Pathway interactions; Policies; Post-Traumatic Stress Disorders; Postmenopause; Pregnancy; Premenopause; Production; Recruitment Activity; Regenerative capacity; Reporting; Research; Research Personnel; Research Project Grants; Research Support; Resources; Risk; Risk Factors; Science; Services; Stem Cell Development; Stress; TNF gene; Testing; Translational Research; United States National Institutes of Health; Universities; Vision; Woman; Women' s Health; age related; antiretroviral therapy; biological sex; bone; cardiovascular health; career; career development; chronic infection; cohort; comorbidity; data management; drug development; early experience; early onset; experience; fracture risk; high risk; hypothalamic-pituitary-adrenal axis; immune activation; improved; microbial host; nervous system disorder; pathogen; programs; prospective; response; sex; social; synergism; therapy development

The overarching goal of the Emory SCORE is to advance the quality of women's health research by leveraging the rich, collaborative and interdisciplinary research environment at Emory University to grow NIH and other extramurally funded research in women's health. The long-term vision is to develop a program at Emory that serves as a regional hub for studying the influence of biological sex on the outcomes of infectious diseases and for promoting the normalization of sex as a biological variable in research with the goal of improving women's health. These goals will be met through a) the implementation of 3 cross-cutting Research Projects employing the “HIV-host pathogen interaction” as a model for probing the influence of sex on the pathology and pathogenesis of infectious diseases; b) the development of a Leadership Administrative Core (LAC); c) the establishment of a Career Enhancement Core (CEC) to foster the career of junior investigators working in women's health research; and d) a Biostatistics Resource Core (BRC) to optimize the rigor of all SCORE- supported research. Our focus on infectious diseases highlights the global burden of these conditions in women, aligns with the priorities of the NIH Office of Women's Health Research (OWHR), and capitalizes on Emory's research strengths in HIV translational research, basic immunology, and anti-viral drug development. The three Research Projects will explore the synergy between HIV induced immune activation and chronic inflammation and that induced by estrogen insensitivity observed in women aging with HIV infection. In the Neuro hypothalamic pituitary adrenal (HPA) axis Project 1 (Drs. Neigh & Michopoulos), we speculate that HIV interacts with multiple factors including stress exposure to decrease systemic estrogen levels and down regulate cellular expressions of estrogen receptors thereby creating relative estrogen insufficiency state with consequent heightening of chronic inflammation in women living with HIV (WLH). Using basic animal models and translational clinical studies, the Musculoskeletal Project 2 (Drs. Weitzmann & Ofotokun) will test the hypothesizes that enhanced fracture risk observed in WLH is due to the collision between HIV/antiretroviral therapy (ART) induced inflammation and that induced by estrogen insufficiency as WLH age with ART. The goal of the Cardiovascular Project 3 (Drs. Quyyumi & Shaw) will be to assess the combined immune effects of HIV and estrogen status described in Project 1 & Project 2 on cardiovascular health as assessed by endogenous reparative/regenerative capacity (circulating progenitor cells) and the development/ progression of sub-clinical coronary (CT angiography) and carotid artery (MRI) atherosclerosis in WLH compared with HIV negative controls. All three projects will examine the same cohort of HIV infected women and HIV negative controls prospectively recruited from active participants at the NIH funded Atlanta WIHS.

Emory SCORE的总体目标是通过利用以下因素来提高女性健康研究的质量： 埃默里大学丰富的合作和跨学科的研究环境， 在女性健康方面的研究长期的愿景是在埃默里大学开发一个项目， 作为研究生物性别对传染病结果影响的区域中心 并促进性作为研究中的生物变量的正常化，以改善 妇女的健康。这些目标将通过a）实施3个横向研究项目来实现 以“HIV-宿主病原体相互作用”为模型探讨性别对病理的影响 传染病的发病机制; B）领导行政核心的发展; c） 成立职业发展核心，以促进初级调查员的职业发展， 妇女健康研究;以及d）生物统计资源核心（BRC），以优化所有SCORE的严格性- 支持研究。我们对传染病的关注突出了这些疾病的全球负担， 妇女，符合妇女健康研究（OWHR）的NIH办公室的优先事项，并利用 埃默里大学在艾滋病毒转化研究，基础免疫学和抗病毒药物开发方面的研究优势。 这三个研究项目将探讨艾滋病毒诱导的免疫激活和慢性 炎症和由雌激素不敏感性引起的，在感染艾滋病毒的老年妇女中观察到。在 神经下丘脑垂体肾上腺（HPA）轴项目1（Neigh和Michopoulos博士），我们推测 艾滋病毒与多种因素相互作用，包括压力暴露，以降低全身雌激素水平， 下调雌激素受体的细胞表达，从而产生相对的雌激素不足状态 从而加剧了HIV感染妇女的慢性炎症（WLH）。使用基本动物 模型和转化临床研究，肌肉骨骼项目2（Weitzmann & Ofotokun博士）将 测试WLH中观察到的骨折风险增加是由于以下因素之间的碰撞的假设 HIV/抗逆转录病毒治疗（ART）诱导的炎症和雌激素不足诱导的WLH年龄 心血管项目3（Quyyumi & Shaw博士）的目标是评估合并的 项目1和项目2中描述的HIV和雌激素状态对心血管健康的免疫影响， 通过内源性修复/再生能力（循环祖细胞）和发育/ WLH亚临床冠状动脉（CT血管造影）和颈动脉（MRI）粥样硬化的进展 与HIV阴性对照相比。这三个项目将检查同一批感染艾滋病毒的妇女 和HIV阴性对照，前瞻性地从NIH资助的Atlanta WIHS的活跃参与者中招募。