What is currently known about this topic? ATAA is a vascular disease characterized by medial degeneration and chronic inflammation. Previous single-cell transcriptomic studies have revealed the cellular heterogeneity of the aortic wall and identified alterations in the populations of smooth muscle, fibroblasts and endothelial cells. However, the immune landscape of ATAA remains unclear. Recent single-cell and spatial analyses of aortic dissections and abdominal aortic aneurysms have revealed dynamic immune remodelling involving macrophage polarization, T-cell activation and cytokine-driven matrix degradation. Nevertheless, the spatial resolution of immune heterogeneity and cross-lineage signalling in human ATAA is poorly understood. What is the key research question? This study aimed to determine the cellular composition, spatial distribution and transcriptional reprogramming of immune cell populations in ATAA and to elucidate how the interactions among immune cells lead to inflammation and pathological remodelling of the aortic wall. What is new? Single-cell RNA sequencing combined with Visium HD spatial transcriptomics can comprehensively characterize the composition, gene expression profiles and spatial localizations of eight types of immune cells in the aortic tissues of the control and ATAA groups at the single-cell level. Targeting of the interferon, AP1, and NF-κB pathways is a novel strategy for treating ATAA. The interactions among immune cells have a synergistic effect during ATAA formation, jointly driving immune remodelling. How might this study influence clinical practice? Elucidation of the dynamic differentiation trajectories and gene expression signatures of distinct immune cell populations in normal and ATAA-affected aortas will enhance our understanding of the immunological mechanisms underlying aneurysm pathogenesis. This knowledge provides a foundation for developing targeted anti-inflammatory therapeutic strategies for ATAA.
Zhen et al. (Wed,) studied this question.