Single-cell profiling of human plaques reveals cellular and molecular signatures of symptomatic atherosclerosis

Symptomatic human carotid plaques show cell-state shifts toward later/terminal osteochondrogenic smooth muscle and CD4 T-cell states, plus inflammatory and EMT transcriptional programs in endothelial, T-cell, and fibroblast populations.

• Why it matters: Vulnerable plaque biology that distinguishes symptomatic from asymptomatic human lesions is still poorly mapped at single-cell resolution, limiting mechanism-driven therapeutic targeting.
• What they did: The study profiled 53 symptomatic and asymptomatic carotid plaques using snRNA-seq (17 samples, 19,100 nuclei) and scRNA-seq (36 samples, 68,983 cells) with independent analyses and meta-analysis across four public datasets.
• The result: Symptomatic plaques had fibroblast depletion with RGS5 downregulation, and genetic risk from coronary/cerebrovascular/peripheral disease was enriched in vascular wall cells; TWIST1, GUCY1A1, and MRAS expression patterns were nominated as candidate driver mechanisms.

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