• Frank M Davis, Lam C Tsoi, Feiyang Ma, Rachael Wasikowski, Bethany B Moore, Steven L Kunkel, Johann E Gudjonsson, and Katherine A Gallagher.
• Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
• Ann. Surg. 2022 Sep 1; 276 (3): 511521511-521.

ObjectiveTo determine cell-specific gene expression profiles that contribute to development of abdominal aortic aneurysms (AAAs).BackgroundAAAs represent the most common pathological aortic dilation leading to the fatal consequence of aortic rupture. Both immune and structural cells contribute to aortic degeneration, however, gene specific alterations in these cellular subsets are poorly understood.MethodsWe performed single-cell RNA sequencing (scRNA-seq) analysis of AAAs and control tissues. AAA-related changes were examined by comparing gene expression profiles as well as detailed receptor-ligand interactions. An integrative analysis of scRNA-seq data with large genome-wide association study data was conducted to identify genes critical for AAA development.ResultsUsing scRNA-seq we provide the first comprehensive characterization of the cellular landscape in human AAA tissues. Unbiased clustering analysis of transcriptional profiles identified seventeen clusters representing 8 cell lineages. For immune cells, clustering analysis identified 4 T-cell and 5 monocyte/macrophage subpopulations, with distinct transcriptional profiles in AAAs compared to controls. Gene enrichment analysis on immune subsets identified multiple pathways only expressed in AAA tissue, including those involved in mitochondrial dysfunction, proliferation, and cytokine secretion. Moreover, receptor-ligand analysis defined robust interactions between vascular smooth muscle cells and myeloid populations in AAA tissues. Lastly, integrated analysis of scRNA-seq data with genome-wide association study studies determined that vascular smooth muscle cell expression of SORT1 is critical for maintaining normal aortic wall function.ConclusionsHere we provide the first comprehensive evaluation of single-cell composition of the abdominal aortic wall and reveal how the gene expression landscape is altered in human AAAs.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

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