Macrophage Migration Inhibitory Factor (MIF) Axis Drives Intracranial Aneurysms Macrophage M1 Polarization: Insights from Single-Cell and Bulk RNA Sequencing

Background: Intracranial aneurysms (IAs) develop and progress through pathological processes, including inflammation and abnormal changes in the vascular structure. The cytokine Macrophage Migration Inhibitory Factor (MIF) is implicated in the pathology of vascular diseases. However, the role of MIF in IAs remains to be elucidated. Methods: This study utilized the Gene Expression Omnibus (GEO) database to analyze samples from IAs and normal arteries. Differential expression of MIF mRNA was assessed via Bulk-RNA sequencing (GSE54083 for testing, GSE75436 for validation), and methylation levels were examined with data from GSE75434. Single-cell transcriptomics (GSE193533) were analyzed using the Seurat package to profile Vascular smooth muscle cells (VSMCs) and macrophages. The CellChat package explored cell communication, particularly between secretory VSMCs and macrophages. Results: Significant upregulation of MIF mRNA was observed in IAs, correlating strongly (r=0.783, p=0.008) with elevated M1-like macrophages, an indication of diagnostic potential. A corresponding decrease in MIF methylation levels and an increase in secretory VSMC proportions were noted. Elevated intercellular MIF signaling suggests it regulates VSMC-macrophage communication, influencing IAs development. Conclusion: Our findings delineate the MIF axis as a pivotal factor in IAs pathogenesis by modulating the activity of secretory VSMCs and M1 macrophages. This axis could present novel therapeutic avenues for managing IAs, potentially stalling progression or serving as adjunctive post-surgical treatment.