Single-Cell Analysis as a Reductionist Approach to Deep Knowledge of Pathogenesis and Pathophysiology of Abdominal Aortic Aneurysm

n abdominal aortic aneurysm (AAA) is a lifethreatening condition marked by aortic wall expansion and weakening, with rupture mortality rate exceeding 80%. 1,2Various factors contribute to AAA onset and progression, including smooth muscle cell (SMC) apoptosis, elastic fiber fragmentation, extracellular matrix (ECM) degradation, and inflammatory cell infiltration. 1However, conventional approaches, including bulk RNA sequencing, provide only an averaged tissue view, limiting our understanding of cellular diversity and interactions within AAA lesions.Single-cell RNA sequencing (scRNA-seq) enables comprehensive analysis of gene expression at the individual cell level, and in recent years, multiple scRNA-seq studies of AAA have unveiled previously unknown cellular characteristics (summarized in the Table ). [3][4]4][5][6][7][8][9] In 2018, Hadi et al.conducted the first scRNA-seq study on experimental AAA induced by angiotensin II infusion in ApoE knockout mice, identifying macrophage-derived Netrin-1 as a key regulator that promotes matrix metalloproteinase-3 upregulation in vascular SMCs, contributing to extracellular matrix degradation and aneurysm development. 3In 2021, Yang et al. performed scRNA-seq on early-stage (day 4 post-induction) murine AAA induced by perivascular application of CaCl2, identifying 12 cell clusters across 8 distinct cell types, including SMCs, fibroblasts, macrophages, B/T lymphocytes, neutrophils, and dendritic cells, which were characterized and compared between AAA and sham groups.