Core C: Human Clinical Cardiovascular and Biostatistics Core

核心 C：人类临床心血管和生物统计学核心

• 批准号: 10334093
• 负责人: Angela M Taylor
• 金额: $ 5.35万
• 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 2022-06-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10334093
• 关键词: Angiography; Area; Arterial Fatty Streak; Atherosclerosis; Basic Science; Biological Assay; Biological Specimen Banks; Biometry; Biostatistics Core; Blood Circulation; Blood Volume; Cardiac Catheterization Procedures; Cardiovascular Diseases; Cardiovascular system; Cell Communication; Cells; Characteristics; Clinical; Coronary; Coronary Angiography; Coronary Arteriosclerosis; DNA; Data; Data Analyses; Development; Freezing; Funding; Future; Genetic; Goals; Human; Immune; Immunity; Individual; Inflammation; Knowledge; Link; Longitudinal cohort; Modeling; Multi-Ethnic Study of Atherosclerosis; Patients; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Population; Program Research Project Grants; Research Design; Research Personnel; Resources; Sampling; Serum; Severities; Shipping; Specimen Handling; Stenosis; System; Techniques; Translations; United States National Institutes of Health; Variant; Work; X-Ray Computed Tomography; atherogenesis; base; burden of illness; calcification; cardiovascular disorder risk; cell bank; cohort; coronary computed tomography angiography; coronary plaque; follow-up; human subject; mouse model; sample collection

Core C Summary 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 Clinical Cardiovascular and Biostatistics Core will provide 3 unique and critical functions to this PPG. The Core will provide large numbers of human cells for functional studies of immune cell populations that are in low abundance in the circulation. These cells will be obtained from patient undergoing cardiac catheterization who are well phenotyped for cardiovascular disease using quantitative coronary angiography and the Gensini scoring system to define disease burden and for variables associated with cardiovascular disease risk. Importantly, this cohort is a long standing cohort supported by this NIH PPG with numerous subjects already banked increasing the power of this cohort. Secondly, the Core will provide a longitudinal cohort of patients with a wide range of atherosclerotic disease who are undergoing coronary computed tomography angiography (coronary CTA). This Core provides the unique expertise to perform advanced techniques allowing for a comprehensive description of coronary plaque presence, stenosis severity, and features of coronary atherosclerosis including plaque size, degree of calcification, positive and negative remodeling, perivascular coronary inflammation, and total atheroma volume. Follow-up coronary CTA studies at 3 years will allow for determination of coronary plaque progression and changes in markers of plaque vulnerability. While this cohort cannot provide the large numbers of immune cells used for functional studies, it will have the ability to provide cells for immune phenotyping, as well as banked cells, serum, and plasma for follow on studies. Finally, the Core will provide biostatistics support for all projects. The functions of the Core will help provide the critical link between plaque characteristics and immune cell phenotypes allowing for a better understanding of how immune cells contribute to plaque development and markers of vulnerability. 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.

核心C摘要 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 动脉粥样硬化的发生和可能的动脉粥样硬化保护。仔细的表型描述是井的翻译的关键 以人类为研究对象的已证实的基础科学假设具有显著的遗传和表型变异 与心血管疾病的小鼠模型相比。大型表型良好的队列和银行标本， 例如动脉粥样硬化的多种族研究(MESA)，允许重要的关联发现将 有免疫力的动脉粥样硬化。然而，这些队列并不提供对后续研究至关重要的大量样本。 有能力定义这种联系背后的机制的功能研究。UVA临床 心血管和生物统计核心将为这个PPG提供3个独特和关键的功能。核心意志 为低丰度免疫细胞群的功能研究提供大量的人体细胞 在流通中。这些细胞将从接受心导管术的患者身上获得，这些患者身体状况良好 应用定量冠脉造影术和Gensini评分系统对心血管疾病进行表型分析 定义疾病负担和与心血管疾病风险相关的变量。重要的是，这群人 是由这位NIH PPG支持的长期队列，许多对象已经被存储在银行中，增加了 这群人的力量。其次，核心将为纵向队列的患者提供广泛的 正在接受冠状动脉CT血管造影术(冠状动脉CTA)的动脉粥样硬化症患者。这 CORE提供独特的专业知识来执行高级技术，从而实现全面的描述 冠状动脉斑块的存在、狭窄程度和包括斑块大小在内的冠状动脉粥样硬化的特征， 钙化程度、正性和负性重构、血管周围冠脉炎症和总动脉粥样硬化 音量。3年后的冠状动脉CTA随访研究将可确定冠状动脉斑块进展 斑块易损性标志物的变化。虽然这个队列不能提供大量的免疫 用于功能研究的细胞，它将有能力为免疫表型提供细胞，以及银行 用于后续研究的细胞、血清和血浆。最后，核心将为所有项目提供生物统计支持。 核心的功能将有助于提供斑块特征和免疫细胞之间的关键联系 表型允许更好地了解免疫细胞如何促进斑块的发展和 易受攻击的标志。该核心将允许将单个项目目标和发现合并到 “共同模式”超越多个小鼠模型，将知识推向终极目标 模特：人类。