Core D: MESA Sample & Data Analysis

核心 D：MESA 样本

• 批准号: 10188603
• 负责人: Stephen S. Rich
• 金额: $ 9.26万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10188603
• 关键词: Acute; Address; Antigens; Apolipoproteins B; Arterial Fatty Streak; Arteries; Atherosclerosis; B-Lymphocyte Subsets; B-Lymphocytes; Biochemistry; Biological; Biological Markers; Biological Models; CD4 Positive T Lymphocytes; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cell Communication; Cell physiology; Cells; Cholesterol; Chronic; Clinical; Data; Data Analyses; Doctor of Philosophy; Equipment and supply inventories; Event; Freezing; Future; Genomics; Goals; Human; Human Resources; Image; Immune; Immune Targeting; Immune response; Immunity; Immunologic Markers; Individual; Inflammatory; Investments; Laboratories; Lipoproteins; Low-Density Lipoproteins; Lymphoid Tissue; Modernization; Molecular Target; Multi-Ethnic Study of Atherosclerosis; Mus; National Heart, Lung, and Blood Institute; Outcome; Participant; Peripheral Blood Mononuclear Cell; Play; Population; Program Research Project Grants; Public Health; Reaction; Regulation; Research Personnel; Resources; Retrieval; Risk Factors; Role; Sampling; Specificity; Statistical Data Interpretation; T-Lymphocyte; Testing; Translational Research; Universities; Vermont; Virginia; Visit; adaptive immune response; apolipoprotein B-100; atherogenesis; biochemical model; cardiovascular risk factor; cellular targeting; chemokine receptor; cohort; coronary artery calcium; coronary calcium scoring; ethnic diversity; experience; follow-up; immune function; immunoregulation; innovation; macrophage; meetings; member; migration; monocyte; new therapeutic target; oxidized low density lipoprotein; success

ABSTRACT (CORE D: MESA Sample and Data Analysis) Cardiovascular disease (CVD) remains a leading cause of death worldwide, despite the success of statins in reducing LDL, a major risk factor for CVD. Immunity is believed to play an important role in atherosclerosis, in which plaque accumulates in the arteries and through its downstream effects, leads to CVD. The importance of various immune cell subsets on atherogenesis in mice have been demonstrated, yet these data are limited on alterations in immune cells during atherogenesis in humans. The goal of the proposed Program Project Grant (PPG) is to identify the regulation of immune cell function by lipoproteins and the crosstalk of these immune cells in human atherogenesis, building on a basis of cellular, biochemical and model system studies. The ultimate goal of these studies is to identify novel therapies targeting immune cell function to limit CVD initiation and progression. The PPG contains four projects that will study functional changes in immune cells and the immune cell cross-talk that occurs during atherosclerosis progression in humans using a well-characterized NHLBI-sponsored longitudinal clinical cohort, the Multi-Ethnic Study of Atherosclerosis (MESA), and the UVA Cardiovascular Cohort. Within the MESA cohort, all projects will utilize data and PBMC samples obtained at baseline (2000-2002), selected on the coronary artery calcium (CAC) score – either low (CAC = 0) or high (CAC > 300). The purpose of Core D (MESA Sample and Data Analysis Core) is to establish the resource of MESA PBMC samples, coordinate the retrieval and use of data from the MESA baseline and follow-up examinations, and participate in the analyses of the immune markers (this PPG) with existing biomarkers and risk factors from MESA. Core D will be used by all projects of the PPG. In order to support the four projects, the specific aims of Core D are to (1) identify the MESA participants meeting critieria (CAC = 0 AU; CAC > 300 AU) with available PBMC samples and with at least two follow-up visits (to permit estimates of progression; (2) receive viable, frozen PBMC samples from the MESA Biochemistry Laboratory at the University of Vermont (Russ Tracy, PhD, Director) and establish an inventory for use by the individual PPG projects; (3) obtain MESA data relevant to the individual projects (biomarkers, risk factors, clinical events, other key variables and outcomes, other markers of immune function) and integrate the existing MESA data with the PPG project data for analysis; and (4) provide support for each PPG project in statistical analyses. Core D leverages the NHLBI investment MESA as a population laboratory with detailed imaging and biological samples and data to merge with the innovative studies of proposed in the PPG in order to advance translational research in limiting the initiation and progression of atherosclerosis that leads to cardiovascular disease.

摘要（核心 D：MESA 样本和数据分析） 尽管他汀类药物在治疗中取得了成功，但心血管疾病（CVD）仍然是全世界死亡的主要原因 降低低密度脂蛋白（CVD 的主要危险因素）被认为在动脉粥样硬化中发挥着重要作用。 斑块在动脉中积聚并通过其下游效应导致 CVD。 小鼠动脉粥样硬化形成中的各种免疫细胞亚群已得到证实，但这些数据仅限于 人类动脉粥样硬化形成过程中免疫细胞的变化。拟议计划项目拨款的目标。 （PPG）的目的是鉴定脂蛋白对免疫细胞功能的调节以及这些免疫细胞的串扰 细胞在人类动脉粥样硬化形成中的作用，建立在细胞、生化和模型系统研究的基础上。 这些研究的最终目标是确定针对免疫细胞功能的新疗法，以限制 CVD 的发生 PPG 包含四个项目，将研究免疫细胞和免疫细胞的功能变化。 使用充分表征的人类动脉粥样硬化进展过程中发生的免疫细胞串扰 NHLBI 赞助的纵向临床队列、动脉粥样硬化多种族研究 (MESA) 和 UVA 心血管队列。在 MESA 队列中，所有项目都将利用在以下时间获得的数据和 PBMC 样本。 基线 (2000-2002)，根据冠状动脉钙 (CAC) 评分选择 – 低 (CAC = 0) 或高 (CAC > 300) 核心 D（MESA 样本和数据分析核心）的目的是建立以下资源： MESA PBMC 样本，协调 MESA 基线和后续数据的检索和使用 检查，并参与免疫标志物（PPG）与现有生物标志物的分析 MESA 的风险因素将被 PPG 的所有项目使用，以支持这四个项目。 核心 D 的具体目标是 (1) 确定 MESA 参与者满足标准（CAC = 0 AU；CAC > 300 AU) 具有可用的 PBMC 样本并至少进行两次随访（以允许估计进展；(2) 从佛蒙特大学 MESA 生物化学实验室接收可行的冷冻 PBMC 样本 （Russ Tracy 博士，主任）并建立供各个 PPG 项目使用的清单 (3) 获得 MESA； 与各个项目相关的数据（生物标志物、风险因素、临床事件、其他关键变量和 结果、免疫功能的其他标志物）并将现有 MESA 数据与 PPG 项目数据整合 进行分析；(4) 为每个 PPG 项目提供统计分析支持。 投资 MESA 作为人口实验室，提供详细的成像和生物样本及数据合并 与 PPG 中提出的创新研究相结合，以推进转化研究，限制 导致心血管疾病的动脉粥样硬化的发生和进展。