Inflammatory and Immune Mechanisms of Atherosclerosis in HIV-Infected Women

HIV感染女性动脉粥样硬化的炎症和免疫机制

• 批准号: 7691229
• 负责人: Robert C Kaplan
• 金额: $ 83.9万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-25 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7691229
• 关键词: Address; Adult; Adverse effects; Affect; African American; Anti-Inflammatory Agents; Anti-inflammatory; Apolipoprotein E; Appearance; Area; Arterial Fatty Streak; Aspirin; Atherosclerosis; Bacterial Translocation; Biological Markers; Biometry; Blood Circulation; Blood Vessels; Blood coagulation; CCR5 gene; CD28 gene; CD4 Lymphocyte Count; CD8B1 gene; Cardiology; Cardiovascular Diseases; Carotid Arteries; Cell Aging; Cell surface; Cells; Chronic; Clinical; Clinical Trials; Coagulation Process; Cohort Studies; Coronary Arteriosclerosis; Coronary heart disease; Cross-Sectional Studies; Data; Data Analyses; Development; Discipline; Disease; Disease Pathway; Elderly; Employee Strikes; Etiology; Event; Fatty acid glycerol esters; Fibrin fragment D; Functional disorder; Goals; Grant; HIV; HIV Infections; HIV Seropositivity; Highly Active Antiretroviral Therapy; Hispanics; Image; Immune; Immune System Diseases; Immunology; Individual; Infection; Inflammation; Inflammation Mediators; Inflammatory; Interdisciplinary Study; Interleukin-10; Interleukin-12; Interleukin-4; Interleukin-6; Internet; Investigation; Leadership; Link; Lipids; Lipoproteins; Longitudinal Studies; Measurement; Measures; Mediator of activation protein; Metabolic; Microbe; Minority; Monitor; Mus; Pathway interactions; Patients; Peripheral; Phase; Phenotype; Play; Population; RNA; Recruitment Activity; Research Infrastructure; Research Personnel; Risk; Risk Factors; Role; Severities; Specimen; Staging; Surface; System; T-Cell Depletion; T-Lymphocyte; Thick; Time; Toxic effect; Ultrasonography; Universities; Ursidae Family; Vascular Diseases; Vermont; Very low density lipoprotein; Viral Load result; Viremia; Woman; Work; abstracting; cardiovascular disorder risk; chemokine; cohort; cytokine; disease phenotype; exhaustion; experience; follow-up; illness length; immune function; improved; innovation; insight; intima media; lipid metabolism; longitudinal design; novel; pathogen; prospective; response; senescence; toll-like receptor 4; virology

DESCRIPTION (provided by applicant): This investigation will examine immune, inflammatory, coagulation, and lipid disturbances as potential mediators of increased atherosclerosis in HIV-infected women participating in the Women's Interagency HIV Study (WIHS). Subjects will include 750 HIV-infected and 250 HIV-uninfected women participating in the Follow-up Phase of the WIHS Carotid Artery Ultrasound Study. The set of specific aims include two primary aims: Aim 1 focuses on established inflammation and coagulation biomarkers as predictors of subclinical atherosclerosis. Aim 2 examines lipid changes which constitute "classic" vascular risk factors. Data analysis goals are: (1) To correlate changes in inflammatory and coagulation markers with HIV disease stage and treatments, including initiation of HAART and changes in viremic and CD4+ status; (2) To determine if immune, inflammatory, and coagulation mechanisms contribute to increased atherosclerosis in HIV-infected women; (3) To determine changes in "classic" vascular risk factors (e.g., lipids) over time due to changes in HAART and HIV disease stage, and how this impacts atherosclerosis. In addition, we propose three exploratory aims examining novel immune and inflammatory mediators that may be of importance to atherosclerosis in HIV-infected adults: 1. Translocation of gut microbes, as measured by 16s RNA; 2. T-cell senescence (CD4+CD28- and CD8+CD28- T-cells); 3. T regulatory cells. This investigation will examine immune, inflammatory, coagulation, and lipid disturbances as potential mediators of increased atherosclerosis in HIV-infected women participating in the Women's Interagency HIV Study (WIHS). We will (1) correlate changes in inflammatory and coagulation markers with HIV disease stage and treatments, including initiation of HAART and changes in viremic and CD4+ status; (2) determine if immune, inflammatory, and coagulation mechanisms contribute to increased atherosclerosis in HIV-infected women; and (3) determine changes in "classic" vascular risk factors (e.g., lipids) over time due to changes in HAART and HIV disease stage, and how this impacts atherosclerosis. (End of Abstract)

描述（由申请人提供）： 这项研究将检查免疫、炎症、凝血和血脂紊乱，作为参与妇女机构间艾滋病毒研究 (WIHS) 的艾滋病毒感染妇女中动脉粥样硬化增加的潜在介质。受试者将包括参与 WIHS 颈动脉超声研究后续阶段的 750 名 HIV 感染者和 250 名 HIV 未感染女性。这组具体目标包括两个主要目标：目标 1 侧重于已建立的炎症和凝血生物标志物作为亚临床动脉粥样硬化的预测因子。目标 2 检查构成“经典”血管危险因素的脂质变化。数据分析目标是： (1) 将炎症和凝血标志物的变化与 HIV 疾病阶段和治疗相关联，包括开始 HAART 以及病毒血症和 CD4+ 状态的变化； (2) 确定免疫、炎症和凝血机制是否会导致感染艾滋病毒的女性动脉粥样硬化加剧； (3) 确定由于 HAART 和 HIV 疾病阶段的变化而导致的“经典”血管危险因素（例如血脂）随时间的变化，以及这如何影响动脉粥样硬化。此外，我们提出了三个探索性目标，检查可能对 HIV 感染成人的动脉粥样硬化具有重要意义的新型免疫和炎症介质： 1. 肠道微生物的易位，通过 16s RNA 测量； 2. T细胞衰老（CD4+CD28-和CD8+CD28-T细胞）； 3.T调节细胞。这项研究将检查免疫、炎症、凝血和血脂紊乱，作为参与妇女机构间艾滋病毒研究 (WIHS) 的艾滋病毒感染妇女中动脉粥样硬化增加的潜在介质。我们将 (1) 将炎症和凝血标志物的变化与 HIV 疾病阶段和治疗相关联，包括开始 HAART 以及病毒血症和 CD4+ 状态的变化； (2) 确定免疫、炎症和凝血机制是否会导致感染艾滋病毒的女性动脉粥样硬化加剧； (3) 确定由于 HAART 和 HIV 疾病阶段的变化而导致的“经典”血管危险因素（例如血脂）随时间的变化，以及这如何影响动脉粥样硬化。 （摘要完）