This study examined cellular composition, transcriptional patterns, and communication networks to develop therapeutic targets. We analyzed single-cell RNA-sequencing data from aortic samples of patients with three common CAPs (including thoracic aortic aneurysm (TAA), abdominal aortic aneurysm (AAA) and chronic thoracic aortic dissection (CTAD)) and controls from the GEO database, validating with independent single-cell data from CTAD patients and controls. Key findings were further validated in experimental studies. Single-cell RNA-sequencing revealed 11 cell clusters in the aortic wall. VSMCs suggested subtype shifts, with fibroblast-like VSMCs expanding and non-classical monocytes enriched in diseased tissues. CellChat analysis predicted potential ligand–receptor interactions involving the ANXA1–FPR1 signaling axis between VSMCs and monocyte-like cells. Pseudotime analysis suggested transitions among VSMC transcriptional states, indicating phenotypic heterogeneity within the VSMC population. SCENIC analysis identified YY1 as a candidate upstream regulator associated with ANXA1-related transcriptional changes. YY1 knockdown increased ROS production and apoptosis, while Ac2-26 reversed these effects. YY1 downregulation is associated with the transition of VSMCs toward a synthetic phenotype. This shift may reduce ANXA1 expression and impair FPR1-related signaling, potentially contributing to the progression through modulation of inflammatory responses.
Xie et al. (Tue,) studied this question.