摘要：SummaryUnstable carotid stenosis is an important cause of ischemic stroke, yet the basis of disease pathophysiology remains largely unknown. We hypothesized that integrated analyses of symptomatic carotid stenosis patients at increased stroke risk stratified by clinical scores, CAR and ABCD2, with transcriptomic and clinical data could improve identification of molecular pathways and targets for instability. We show that high CAR score reflects plaque instability processes related to intra-plaque hemorrhage, angiogenesis, inflammation, and foam cell differentiation, whereas ABCD2 associates with neutrophil-mediated immunity, foam cell differentiation, cholesterol transport, and coagulation. Repressed processes in plaques from high-risk patients were ossification, chondrocyte differentiation, SMC migration, and ECM organization.ABCB5gene was found as the top upregulated in high-risk patient’s plaques, localized to macrophages in areas with neovascularization and intra-plaque hemorrhage. The link betweenABCB5and intra-plaque hemorrhage suggests its key role for plaque instability that warrants further exploration.Graphical abstractDisplay OmittedHighlights•We integrated stroke risk in carotid stenosis patients with plaque transcriptomics•High CAR and ABCD2 scores reflect plaque instability processes and hemorrhage•ABCB5is upregulated in high-risk plaques, macrophages, and around neovessels•CAR and ABCD2 capture vulnerable plaque features and improve risk stratificationHealth sciences; Transcriptomics; Cell biology
