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） 心血管疾病（CVD）仍然是全球死亡的主要原因，dospite汀类药物在 减少LDL，这是CVD的主要危险因素。据信免疫在动脉粥样硬化中起重要作用， 牙菌斑积聚在动脉及其下游作用中，导致CVD。重要性 已经证明了小鼠动脉粥样硬化的各种免疫细胞亚群，但这些数据受到限制 人类动脉粥样硬化期间免疫细胞的改变。拟议的计划项目赠款的目标 （PPG）是确定脂蛋白对免疫细胞功能的调节和这些免疫的串扰 人动脉粥样硬化中的细胞，基于细胞，生化和模型系统研究的基础。 这些研究的最终目标是确定针对免疫细胞功能以限制CVD启动的新型疗法 和进展。 PPG包含四个项目，这些项目将研究免疫细胞的功能变化和 免疫细胞串扰，在人类动脉粥样硬化进展过程中使用良好的特征 NHLBI赞助的纵向临床队列，动脉粥样硬化的多种族研究（MESA）和UVA 心血管队列。在MESA队列中，所有项目都将利用在 基线（2000-2002），在冠状动脉钙（CAC）评分上选择 - 低（CAC = 0）或高 （CAC> 300）。核心D的目的（MESA样本和数据分析核心）是建立 MESA PBMC样品，协调台基线和随访的数据的检索和使用 检查并参与现有生物标志物的免疫标记（此PPG）的分析 MESA的危险因素。核心D将由PPG的所有项目使用。为了支持这四个项目， 核心D的具体目的是（1）确定遇到Critieria的MESA参与者（CAC = 0 AU; CAC> 300 AU）可提供可用的PBMC样品，并至少进行两次随访（以允许进行进展；（2） 从佛蒙特大学的MESA生物化学实验室接收可行的冷冻PBMC样品 （Russ Tracy，PhD，董事）并建立了一个库存，以供各个PPG项目使用； （3）获取台面 与各个项目有关的数据（生物标志物，风险因素，临床事件，其他关键变量以及 结果，免疫功能的其他标记），并将现有的台面数据与PPG项目数据集成 用于分析； （4）在统计分析中为每个PPG项目提供支持。核心D利用NHLBI 投资台面作为人口实验室，具有详细的成像和生物样品以及数据合并 通过对PPG提出的创新研究，以推动转化研究限制 导致心血管疾病的动脉粥样硬化的起始和进展。