Single-Cell Transcriptomics of Human Pericarotid Lymph Nodes Indicating Stability of Carotid Atherosclerotic Plaques.

BACKGROUND: The link between lymph node (LN) function and atherosclerosis is unclear, especially at the single-cell level. This study explores the relationship between pericarotid LNs and plaque stability using single-cell transcriptome analysis. METHODS: We enrolled 106 patients with severe internal carotid artery stenosis undergoing carotid endarterectomy. We recorded baseline clinical data and pericarotid LN size, and analyzed plaque composition to assess its association with enlarged LNs. Single-cell transcriptome and T/B-cell receptor sequencing were used to profile pericarotid LNs. RESULTS: Patients with symptomatic carotid atherosclerosis had more enlarged pericarotid LNs (P<0.001), indicating plaque instability. This was characterized by increased inflammation, greater CD68(+) macrophage infiltration (P<0.001), and reduced fibrous content (P<0.001). Single-cell analysis identified 3 main cellular compartments: lymphocytes, myeloid cells, and stromal cells. Enlarged LNs had significantly more naive B and T cells (P<0.001), suggesting heightened immune response. Macrophages and neutrophils may help in cholesterol transport and degradation, while stromal cells may regulate the immune microenvironment by influencing T-cell tolerance and lymphocyte trafficking. CONCLUSIONS: Enlarged pericarotid LNs are potential biomarkers for plaque instability and recent ischemic events. This study provides a comprehensive single-cell transcriptomic landscape of human LNs in atherosclerosis.