Core D: MESA Sample & Data Analysis

摘要（核心D：梅萨样本和数据分析） 心血管疾病（CVD）仍然是全球死亡的主要原因，尽管他汀类药物在治疗心血管疾病方面取得了成功。 降低低密度脂蛋白，这是心血管疾病的主要危险因素。免疫被认为在动脉粥样硬化中起重要作用， 斑块在动脉中积聚并通过其下游效应导致CVD。的重要性 已经证明了小鼠中各种免疫细胞亚群对动脉粥样硬化形成的影响，然而这些数据仅限于 在人类动脉粥样硬化形成过程中免疫细胞的改变。计划项目补助金的目标 (PPG)目的是确定脂蛋白对免疫细胞功能的调节以及这些免疫细胞之间的相互干扰， 细胞在人类动脉粥样硬化形成中的作用，建立在细胞、生物化学和模型系统研究的基础上。的 这些研究的最终目标是确定靶向免疫细胞功能的新疗法，以限制CVD的发生 和进步。PPG包含四个项目，将研究免疫细胞的功能变化， 免疫细胞的串扰发生在人类动脉粥样硬化的进展，使用一个良好的表征， NHLBI申办的纵向临床队列、多种族动脉粥样硬化研究（梅萨）和UVA 心血管队列。在梅萨队列中，所有项目都将利用在以下时间点获得的数据和PBMC样本： 基线（2000-2002年），根据冠状动脉钙（CAC）评分选择-低（CAC = 0）或高 (CAC> 300）。核心D（梅萨样本和数据分析核心）的目的是建立 梅萨PBMC样本，协调梅萨基线和随访数据的检索和使用 检查，并参与现有生物标志物的免疫标志物（此PPG）分析， 梅萨的风险因素。核心D将用于项目编制补助金的所有项目。为了支持这四个项目， 核心D的具体目标是：（1）确定梅萨参与者满足标准（CAC = 0 Au; CAC > 300 Au），具有可用的PBMC样本，并且具有至少两次随访访视（以允许估计进展;（2） 从佛蒙特大学的梅萨生物化学实验室接收活的冷冻PBMC样本 (Russ Tracy博士，主任），并建立一个清单，供各个PPG项目使用;（3）获得梅萨 与单个项目相关的数据（生物标志物、风险因素、临床事件、其他关键变量和 结果，其他免疫功能标志物），并将现有梅萨数据与PPG项目数据整合 （4）为每个PPG项目的统计分析提供支持。核心D利用NHLBI 投资梅萨作为一个人口实验室与详细的成像和生物样本和数据合并 与PPG中提出的创新研究，以推进限制 导致心血管疾病的动脉粥样硬化的开始和进展。

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.