Core C: UVA Cardiovascular Cohort

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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.