Abstract 15542: Immuno-Footprint of Myeloid Clusters in Human Abdominal Aortic Aneurysm

• Published in: Circulation (New York, N.Y.) N.Y.), 2022-11, Vol.146 (Suppl_1), p.A15542-A15542
• Main Authors: Silvestro, Michele, Rivera Martinez, Cristobal, Vlahos, John, Pratama, Muhammad Yogi, Kumari, Puja, Sleiman Tellaoui, Rayan, Maldonado, Thomas, Ramkhelawon, Bhama
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.146.suppl_1.15542

Inflammation is a hallmark of abdominal aortic aneurysms (AAA) with central roles ascribed to myeloid lineage effector cells. However, the dynamics of circulating immune subsets, their interaction, and direct roles in AAA are not completely understood. Here, in human AAA and control blood, we used unbiased Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITEseq) to investigate the complex spectrum of the proteome and transcriptome of the immune population, with refined characterization of immune subtypes in the peripheral blood. We also performed matched CITEseq for AAA tissues, allowing to define the fate and immuno-footprint of distinct immune clusters from blood to tissue. Fresh aortic specimens and blood from patients undergoing open AAA repair (n=5) and from healthy donors (n=2) were processed for CITEseq with a panel of antibodies encompassing 15 biologically relevant immune cell surface markers. After alignment, demultiplexing and cell cluster identification, analysis of proteo/transcriptome was performed in peripheral blood and in paired aneurysmal tissue datasets. Unsupervised clustering of CITEseq datasets from peripheral blood revealed eleven distinct clusters, with a unique signature of FCGR3A/CD16+CD14/CD14lo monocytic populations in AAA patients, showing characteristics of myeloid-derived suppressor cells. Interestingly, we also unveiled that a subset of pro-inflammatory monocytes coerced solidly with activated platelets in monocyte-platelet complexes (MPC). MPC were selectively accrued in the blood of AAA. Pairwise analysis of blood and aortic tissue revealed increased accumulation of CD14/CD14+ but not FCGR3A/CD16+ cells in AAA wall. In murine AAA modeled by angiotensin II infusion in ApoE-/- mice, we observed increased MPC in the circulation which correlated with increased inflammation in the aortic tissue. We further demonstrated that monocytes that bind to platelets are derived from the spleen. Splenectomy abrogated the formation of MPC and protected from AAA development in mice, similarly to targeted disruption of MPC. Here we show that interference with unbalanced circulating myeloid subsets and disruption of MPC are novel attractive avenues for therapeutic strategies in AAA.