Identification and Validation of TREM2 in Intracranial Aneurysms

Intracranial aneurysm (IA) is a cerebrovascular disease that seriously endangers human heath and life. However, the pathogenesis of IA has not been clarified. In this study, we explored the role of the triggering receptor expressed on myeloid cells-2 (TREM2) gene to explore a novel mechanism underlying IA. First, we verified the role of the candidate gene, TREM2 in a modified mouse model of IA. Second, we verified elevated expression of TREM2 using the Gene Expression Omnibus (GEO) database (GSE54083 and GSE75436) and developed protein interaction (PPI) network analysis using the top one hundred DEGs from GSE75436 dataset. Finally, we predicted a likely mechanism by which TREM2 is involved in the pathology of IA using single-gene Gene Set Enrichment Analysis (GSEA). The expression of TREM2 and inflammatory factors was significantly increased in the modified mouse IA model, and showed a positive correlation. Elevated expression of TREM2 was also found in IA patients tissues from the GSE54083 and GSE75436 data sets. PPI network analyses suggested that the DEGs were involved in a variety of inflammatory processes. The GSEA results suggest that TREM2 may participate in IA progression by regulating macrophage function. TREM2 is highly expressed in both human and mouse IA tissues, and may participate in IA progression by regulating macrophage function and inflammatory factor expression. The molecular mechanism of TREM2 involvement in the IA process can be further studied using our modified mouse IA model.