Revealing FPR1 as a potential pathogenic biomarker for aortic dissection based on Mendelian randomization, single-cell transcriptome and clinical data analysis.

BACKGROUND: Aortic dissection is characterized by immune cell infiltration and vascular inflammation, yet its molecular mechanisms remain unclear. This study investigates the role of immune-related genes in AD pathogenesis. METHODS: We integrated Mendelian randomization and transcriptomic analyses to identify AD-associated genetic risk genes. Immune infiltration and functional enrichment analyses were applied to explore monocyte and neutrophil involvement. Key genes were validated in human and mouse aortic tissues, and FPR1’s role was assessed using Cyclosporin H treatment. Clinical correlation between FPR1 expression and prognosis was evaluated. RESULTS: Eight highly differentially expressed genes were identified, with FPR1 showing predominant expression in myeloid cells. Single-cell and bulk RNA-seq revealed immune cell accumulation in AD tissues, where FPR1 correlated with monocyte/neutrophil activation and enhanced vascular inflammation. FPR1 upregulation in AD tissues accompanied increased neutrophil activation markers (TNF-α, IL-1β, IL-6, CCL2). FPR1 inhibition suppressed ERK1/2 pathway activation, reduced IL-1β production, and attenuated AD severity in mice. Clinically, elevated FPR1 levels were associated with disease severity and predicted poor postoperative outcomes, with significantly higher expression in 30-day non-survivors. CONCLUSION: FPR1 plays a critical role in AD pathogenesis by promoting myeloid immune cell activation and vascular inflammation, highlighting its potential as a therapeutic target and prognostic biomarker. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-026-00732-4.