Abstract 1013: Intense Impact Of Interleukin 1B Expressing Inflammatory Macrophages In Acute Aortic Dissection

Abstract

Background: There is no treatment for acute aortic dissection (AAD) targeting inflammatory cells. We aimed to identify specific inflammatory cells associated with AAD and identify new therapeutic targets. Methods: We characterized the specific distribution of myeloid cells of both human type A AAD samples and a murine AAD model generated using angiotensin II (ANGII) and β-aminopropionitrile (BAPN) by single-cell RNA sequencing (scRNA-seq). We also examined the effect of an anti-interleukin-1β (IL-1β) antibody in the murine AAD model. Results: The proportion of IL1B + inflammatory macrophages and classical monocytes were increased in human AAD samples. Trajectory analysis demonstrated that IL1B + inflammatory macrophages uniquely observed in the aorta of AAD differentiated from S100A8/9/12 + classical monocytes. In addition, inflammatory macrophages that stained positively for both IL-1β and CD68 accumulated in the false lumen of the adventitia. In parallel, we found increased infiltration of neutrophils and monocytes with the expression of cytokines, such as IL-1β, in the aorta and accumulation of inflammatory macrophages, derived from infiltrating monocytes, before the onset of macroscopic AAD in the murine AAD model. Finally, to investigate the association between IL-1β mainly derived from monocytes and IL1B + inflammatory macrophages, we conducted blocking experiments using an anti-IL-1β antibody. Anti-IL-1β antibody improved survival by preventing elastin degradation. Conclusions: We observed the accumulation of inflammatory macrophages expressing IL-1β in both human AAD samples and in a murine AAD model. Anti-IL-1β antibody could improve the mortality rate in mice, suggesting that it may be a treatment option for AAD.