Spatial transcriptomic analysis reveals spatial features in human Stanford type A aortic dissection

Stanford type A aortic dissection (AAD) is a life-threatening cardiovascular disease characterized by tearing in the aortic wall. Using spatial transcriptomics and multiplex immunofluorescence, we comprehensively analyzed ascending aortas from eight AAD patients across different severities and segments. We demonstrate that SPP1-driven inflammatory signaling intensifies with AAD severity, identifying a nine-gene, layer-anchored severity scale: MYL6/CALD1/MYH9 (mild); CCL2/CP/COL4A1 (moderate); and TMSB4X/ATP5F1E/PKM (severe). Importantly, the collagen-remodeling triad COL1A1/COL3A1/MMP2 is concurrently up-regulated in the brachiocephalic, left subclavian, and left common carotid arteries, often before the ascending aorta meets surgical diameter thresholds. These molecular signatures provide a critical foundation for non-invasive biomarker discovery, risk stratification, and precision pharmacotherapy targeting the SPP1-inflammatory axis, ultimately offering new insights into AAD mechanisms and therapeutic targets.