Abstract / Summary
Background/Objectives: Aortic aneurysm (AA) involves inflammatory recruitment and vascular smooth muscle cell (VSMC) remodeling, but the cellular contribution of candidate chemokine receptors remains unclear. We prioritized reproducible AA-associated genes, localized their cellular sources, and tested whether monocyte CCR2 influences human aortic smooth muscle cells (HASMCs). Methods: Differentially expressed genes shared by GSE57691 and GSE7084 underwent enrichment, protein–protein interaction, regulatory-network, and drug–gene analyses. Hub genes were assessed in GSE9106 and localized in GSE166676 single-cell RNA-sequencing data. CCR2-silenced THP-1 monocytic cells were indirectly co-cultured with HASMCs. CCR2 knockdown was verified by quantitative PCR; HASMC remodeling-related proteins and 24-h scratch-wound closure were evaluated. Results: We identified 107 common upregulated genes and ten immune-related hubs. CCR2 was monocyte-enriched and higher in AA cells overall (p = 0.00799) and AA monocytes (p = 0.00440). THP-1 co-culture increased COL3A1 and SPP1, decreased α-SMA and TPM, and increased HASMC wound closure. CCR2 silencing partially reversed these changes and decreased wound closure versus siNC-THP-1 cells (p < 0.01). Conclusions: Multi-omic evidence and non-contact co-culture support CCR2-dependent monocyte–HASMC paracrine crosstalk in AA-associated remodeling. The responsible mediators and in vivo relevance require further study.