Abstract

Background: Carotid atherosclerosis (CAS) is a key cause of ischemic stroke that is strongly associated with increased risks of cardiovascular disease and vascular death, hence the urgent need to develop therapeutic strategies targeting carotid atherosclerotic plaques that would reduce the overall risk of cerebrovascular events.

Aims: This study performs single-cell sequencing to dissect the cellular subpopulations in CAS. Molecular docking is used to uncover the potential therapeutic targets, consequently providing a theoretical basis for the CAS treatment strategies.

Study Design: Integrated single-cell, spatial transcriptomic and molecular docking analysis.

Methods: The single-cell sequencing data were retrieved from the Gene Expression Omnibus. Enrichment analyses were performed to characterize the cellular subpopulation functions. Accordingly, cell-cell communication networks were mapped to uncover the inter-subgroup interactions. Molecular docking was also employed to identify the potential therapeutic targets.

Results: In this study, we identified the multiple cellular subpopulations that are associated with CAS. These CAS-related subpopulations engage in intercellular communication via distinct signaling pathways. Cannabidiol exhibits strong binding affinities for the macrophage, endothelial, and vascular smooth muscle cell markers. Spatial transcriptomics revealed that ACTC1, AKR1C2, and FABP4 exhibit region-specific expression patterns within the plaque.

Conclusion: Dissecting the diverse cellular subpopulations in CAS and elucidating their functions and mechanisms, this study integrates single-cell sequencing, molecular docking, and spatial transcriptomics to offer fresh insights into CAS therapy.