Investigation for atherosclerotic plaque rupture with thrombosis in mice based on single-cell sequencing and bioinformatics analysis.

Introduction: Atherosclerotic plaque rupture with thrombus formation leads to severe cardiovascular events. We hoped to explore the hub genes providing critical roles in the process of atherosclerotic plaque rupture accompanied by thrombus formation, which might provide a new research direction for clinical therapy. Methods: The mouse model of atherosclerotic plaque rupture with thrombosis was established by the combined ligation of the left renal artery and common carotid artery, while key genes and regulatory pathways were identified using single-cell RNA sequencing and bioinformatics analysis. Results: The mice model accompanied by atherosclerotic plaque rupture with thrombus formation was successfully established. Seventeen cell subsets were identified based on scRNA-seq analysis including Fibroblasts. Downstream analysis showed 376 TDEGs were revealed to be closed associated with thrombosis-prone plaques. These TDEGs were mainly enriched in cell adhesion. A total of five hub genes including COL5A1, VCAN, PTGS2, ITGAV, and ITGA8 were investigated. Drug-gene interaction network analysis identified several drug-gene relations, such as Aspirin-PTGS2. Fibroblasts might play a vital role in atherosclerotic plaque rupture with thrombosis. Discussion: COL5A1, VCAN, PTGS2, ITGAV and ITGA8 might be novel biomarkers for atherosclerotic plaque rupture with thrombosis. ITGAV and VCAN might take part in the process atherosclerotic plaque rupture with thrombosis via cell adhesion function.