Core C: UVA Cardiovascular Cohort

摘要（核心C：UVA心血管队列） 免疫细胞变异对人类动脉粥样硬化的影响是一个知之甚少的领域， 动脉粥样硬化形成和可能的动脉粥样硬化保护。仔细的表型描述对于良好的翻译至关重要- 已被证实的基本科学假设进入人类受试者，因为人类具有显著的遗传和表型 与心血管疾病的鼠模型相比的变化。大型表型良好的队列， 标本，如动脉粥样硬化的多民族研究（梅萨），允许重要的关联 发现动脉粥样硬化与免疫力有关。然而，这些队列并不提供大量 对于后续功能研究至关重要的样本，这些研究能够确定 协会UVA心血管队列将通过获得等同于 在冠状动脉钙（CAC）测量和临床变量方面，表型与梅萨相同 与心血管疾病相关的外周血单核细胞 （PBMC）用于后续研究。核心研究将提供从心脏研究中入组的患者子集。 由于各种原因接受心导管插入术的导管插入术实验室，从而提供了一个 具有广泛疾病负担的人群，因此可以在无疾病负担的受试者中进行后续研究。 病到重症。心血管风险组将根据CAC测量结果进行分配， 根据梅萨中使用的方法，计算FRA风险评分和梅萨风险评分。此外，本发明还 所有受试者都将进行定量冠状动脉造影（QCA），使用Genisini评分作为第二个 衡量疾病负担。核心将为本PPG提供三个具体的关键功能：1.提供 基于梅萨队列提供的初始CyTOF和RNAseq研究， 对于所有项目，2.）为功能研究提供大量外周血单核细胞（PBMC） 在所有项目的循环中丰度低的免疫细胞中，以及3.）为项目2提供血浆 和4）进行项目2和3的B细胞功能分析的特定测定。因此，Core 3不仅 对于进一步理解梅萨中揭示的关联机制至关重要， 将在每个个体中研究的鼠发现投射到人类模型中。该核心将允许合并 将各个项目目标和发现转化为“共同模型”，超越了多种小鼠模型， 将知识推进到最终的目标模型：人类。

ABSTRACT (CORE C: UVA Cardiovascular Cohort) The effect of immune cell variations on atherosclerosis in humans represents a poorly understood area of atherogenesis and possible atheroprotection. Careful phenotypic description is critical for translation of well- proven basic science hypotheses into human subjects as humans have marked genetic and phenotypic variation compared to murine models of cardiovascular disease. Large well-phenotyped cohorts with banked specimens, such as the Multi-Ethnic Study of Atherosclerosis (MESA), allow for important associative discoveries linking atherosclerosis with immunity. However, these cohorts do not provide large volume samples critical for follow-on functional studies that have the ability to define the mechanisms underlying the association. The UVA Cardiovascular Cohort will provide for this important aspect by obtaining equivalent phenotyping as in MESA in terms of coronary artery calcium (CAC) measurements and clinical variables associated with cardiovascular disease on subjects that have additional peripheral blood mononuclear cells (PBMCs) banked for follow-on studies. The Core will provide a subset of patients enrolled from the cardiac catheterization laboratories who undergo cardiac catheterization for a variety of reasons, thus providing a population with a wide range of disease burden so that follow on studies can be performed in subjects with no disease to severe disease. Cardiovascular risk groups will be assigned based on CAC measurements, Framingham risk scores, and MESA Risk Scores in accordance with methodology used in MESA. Additionally, all subjects will have quantitative coronary angiography (QCA) reported using the Genisini score as a second measurement of disease burden. The Core will provide three specific, critical functions to this PPG; 1.) provide human cells for functional assays based on initial CyTOF and RNAseq studies provided by the MESA cohort for all projects, 2.) provide large numbers of peripheral blood mononuclear cells (PBMCs) for functional studies in immune cells that are in low abundance in the circulation for all projects, and 3.) provide plasma to Project 2 and 4) perform specific assays for functional analysis of B cells for Projects 2 and 3. Thus, Core 3 will not only be critical to further understanding the associative mechanisms uncovered in MESA, but also to advancing murine findings studied in each individual project into the human model. This Core will allow for incorporation of individual project goals and discoveries into a “common model” moving beyond multiple murine models and advancing knowledge into the ultimate target model: the human.