Core D: MESA Sample & Data Analysis

摘要(核心D：MESA样本和数据分析) 心血管疾病(CVD)仍然是全球主要的死亡原因，尽管他汀类药物在 降低低密度脂蛋白，这是心血管疾病的主要风险因素。免疫被认为在动脉粥样硬化中起着重要作用 这种斑块聚集在动脉中，并通过其下游作用，导致心血管疾病。重要的是 各种免疫细胞亚群在小鼠动脉粥样硬化形成中的作用已被证实，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。拟议方案项目赠款的目标 (Ppg)是识别脂蛋白对免疫细胞功能的调节以及这些免疫的串扰。 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。这个 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的启动 和进步。PPG包含四个项目，将研究免疫细胞的功能变化和 在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 心血管疾病队列。在MESA队列中，所有项目都将使用在以下位置获得的数据和PBMC样本 基线(2000-2002)，根据冠状动脉钙化(CAC)评分选择--低(CAC=0)或高 (CAC&GT；300)。核心D(MESA样本和数据分析核心)的目的是建立 MESA PBMC样本，协调MESA基线和后续行动中数据的检索和使用 检查，并参与免疫标记物(此PPG)与现有生物标记物和 来自梅萨的风险因素。核心D将被PPG的所有项目使用。为了支持这四个项目， 核心D的具体目标是(1)确定符合标准的MESA参与者(CAC=0AU；CAC&GT；300 Au)有可获得的PBMC样本，并至少有两次后续访问(以估计进展情况；(2) 从佛蒙特州大学梅萨生物化学实验室接收可存活的冷冻PBMC样本 (Russ Tracy，博士，主任)，并建立供个别PPG项目使用的清单；(3)获得MESA 与个别项目相关的数据(生物标志物、风险因素、临床事件、其他关键变量和 结果、免疫功能的其他标记物)，并将现有的MESA数据与PPG项目数据相结合 用于分析；以及(4)在统计分析方面为每个PPG项目提供支持。核心D利用NHLBI 投资台作为一个人口实验室，拥有详细的成像和生物样本以及要合并的数据 随着PPG中提出的创新性研究，以推动翻译研究在限制 动脉粥样硬化的开始和发展，导致心血管疾病。

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.