Abstract 10612: Immune Cells in Calcific Aortic Valve Disease

Introduction: Calcific aortic valve disease is a multifaceted disease in which pathogenic mineralisation of the valvular tissue occurs in tandem with fibrocalcific remodelling of the aortic valve, resulting in a wide variety of clinical presentations. Immunity, both innate and adaptive have been shown to play important roles in chronic cardiovascular diseases. Noteably, 15% of cells within healthy aortic valves are up to hematopoietic origin and these populations are further increased within calcified valves however, the role of the immune system within CAVD remains to be elucidated. Objectives: Investigate the prevalence and distribution of immune cells within CAVD. Methods & Results: Human calcified aortic heart valves were obtained from valve replacement surgeries. Immunohistological assessment of immune cells within the tissue was conducted, with the presence of T cells, B cells, macrophages and dendritic cells detected in the vicinity of calcific nodules. Flow cytometry analysis of cells isolated from the valve was conducted. 69% of cells isolated from the valve were CD45+, with 57% and 42% of CD45+ CD3+ presenting as CD8+ and CD4+ respectively. Within the CD8+ population, 56% of these were central memory CD8+ T cells, with 24% as activated CD8+ T cells. Likewise, within the CD4+ population 29.5% CD4+ cells were activated T cells and 55% central memory T cells. Small populations of naïve CD4+ and CD8+ T cells; 9% and 13% respectively, were present within the valve. CD45+, CD3+, CD4+/CD8+ cells were isolated via FACS and their global proteomic profile was analysed on the Thermo Scientific Lumos orbitrap mass spectrometer. IL-31RA was present within the T cell population, alongside MAPK pathway mediators were also present. Network analysis of T cell proteomics showed increased IL-4 and IL-13 pathways (p<0.01) indicative of a Type II inflammatory pathway, correlating with the presence of basophils and eosinophils present within the valve. Conclusions: Prevalence of immune cells within the valve suggests an inflammatory role in the development of calcific aortic valve disease, with the prevalence of T cells within the valve suggesting an adaptive immune response may be central to the pathology of CAVD.