Core C: UVA Cardiovascular Cohort

核心 C：UVA 心血管队列

• 批准号: 10188602
• 负责人: Angela M Taylor
• 金额: $ 22.65万
• 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/10188602
• 关键词: Area; Atherosclerosis; B-Lymphocyte Subsets; B-Lymphocytes; Basic Science; Binding; Biological Assay; Biological Specimen Banks; Blood Circulation; Blood specimen; Cardiac Catheterization Procedures; Cardiovascular Diseases; Cardiovascular system; Cell Communication; Cell Survival; Cells; Cholesterol Esters; Clinical; Cohort Effect; Coronary Angiography; DNA; Data; Disease; Enrollment; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Freezing; Genetic; Goals; Human; Immune; Immunity; Immunoglobulin M; Incubated; Individual; Knowledge; Laboratories; Link; Low-Density Lipoproteins; Measurement; Measures; Methodology; Modeling; Multi-Ethnic Study of Atherosclerosis; Mus; Patients; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Population; Preparation; Program Research Project Grants; Reporting; Research Personnel; Resources; Risk; Risk Factors; Running; SNP genotyping; Sampling; Serum; Surface; Testing; Time; Translations; Variant; Work; atherogenesis; atherosclerosis risk; base; burden of illness; cardiovascular risk factor; cell bank; cell preparation; cohort; coronary artery calcium; enzyme linked immunospot assay; human model; human subject; lipoprotein cholesterol; mouse model; patient subsets; transcriptome sequencing

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.

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翻译至关重要 由于人类具有标记的遗传和表型，因此已在人类受试者中证明了基础科学假设 与心血管疾病小鼠模型相比的差异。大量表型良好的队列 动脉粥样硬化的多种族研究 (MESA) 等样本允许重要的联想 将动脉粥样硬化与免疫力联系起来的发现。然而，这些群体并不能提供大量的 对于后续功能研究至关重要的样本，能够定义潜在的机制 协会。 UVA 心血管队列将通过获得等效的信息来实现这一重要方面 与 MESA 中的冠状动脉钙 (CAC) 测量和临床变量一样进行表型分析 对于具有额外外周血单核细胞的受试者，与心血管疾病相关 （PBMC）储存用于后续研究。核心将提供一部分从心脏科入组的患者 因各种原因进行心导管检查的导管实验室，从而提供了 具有广泛疾病负担的人群，以便可以在没有疾病负担的受试者中进行后续研究 疾病到严重疾病。心血管风险组将根据 CAC 测量值进行分配， Framingham 风险评分和 MESA 风险评分（根据 MESA 使用的方法）。此外， 所有受试者都将进行定量冠状动脉造影 (QCA) 报告，使用 Genisini 评分作为第二评分 疾病负担的测量。核心将为该 PPG 提供三个特定的关键功能： 1.) 提供 基于 MESA 队列提供的初始 CyTOF 和 RNAseq 研究，对人类细胞进行功能测定 对于所有项目，2.) 提供大量外周血单核细胞 (PBMC) 用于功能研究 所有项目循环中丰度较低的免疫细胞中，以及 3.) 为项目 2 提供血浆 4) 对项目 2 和 3 进行 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 MESA 中发现的关联机制至关重要，而且对于推进 在每个单独项目中研究的小鼠研究结果都融入到人类模型中。该核心将允许合并 将各个项目目标和发现纳入“通用模型”，超越多种小鼠模型， 将知识推进到最终目标模型：人类。