AP-1 Dominated Coronary Inflammation as the Pivotal Culprit Causing Recurrent in-stent Restenosis

ABSTRACT: Aims: Recurrent in-stent restenosis (RISR) represents a series of repeated cardiac ischemic events post-successful revascularization, associated with exceedingly huge disease burden without effective pharmacologic therapies. Neointimal hyperplasia (NIH) is recognized as the primary biological driver that fundamentally triggers restenosis, yet the underlying immune mechanisms governing smooth muscle cell (SMC) phenotypic transitions remain unclear. Methods：Coronary blood samples from ten RISR patients and ten control individuals were subjected to single-cell RNA sequencing (scRNA-seq). Key pathogenic targets and pathways were identified through comprehensive bioinformatics analyses and further validated via in vitro experiments with monocytes isolated from the validation cohort using flow cytometry. Results: Here, scRNA-seq analysis revealed the prominent role of monocytes in driving RISR progression, with activator protein-1 (AP-1) genes emerging as core differentially expressed genes (DEGs). In vitro experiments within monocytes further demonstrated that the CCL5-CCR1/p38 MAPK pathway acts as an upstream regulatory axis of AP-1, promoting the release of inflammatory cytokines and ultimately inducing a phenotypic switch in vascular smooth muscle cells (VSMCs). Additionally, a novel monocyte subtype was identified in coronary blood and the distinct alterations of subtype composition were specifically observed throughout the progress of RISR. Conclusion: This study provides the first comprehensive immunological landscape of RISR, thus offering theoretical support for clinical interventions. Upregulation of the CCR1/p38 MAPK/AP-1/cytokine axis in monocytes was identified as a critical mechanism facilitating the occurrence and progression of RISR.

ORGANISM(S): Homo sapiens

PROVIDER: GSE283461 | GEO | 2026/10/14

REPOSITORIES: GEO