Core C: Human Clinical Cardiovascular and Biostatistics Core

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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.