Altered expression patterns of glutamate decarboxylases in peripheral blood of intracranial aneurysm patients: Implications for aneurysm pathogenesis and progression.

OBJECTIVE

To investigate the expression levels of GAD1 and GAD2 in the peripheral blood of intracranial aneurysm (IA) patients and their correlation with the occurrence and development of IA.

METHODS

Relevant IA datasets were retrieved from the Gene Expression Omnibus (GEO) database, and the limma package was employed to identify differentially expressed genes (DEGs) between IA wall tissues and superficial temporal artery wall tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the identified DEGs. A total of 52 IA patients were enrolled in the IA group, and 34 healthy individuals were included in the healthy control (HC) group. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to measure the expression levels of GAD1 and GAD2 in the peripheral blood of IA patients. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were utilized to evaluate the predictive value of GAD1 and GAD2 for IA. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of TNF-α, IL-6, and IL-1β in both groups.

RESULTS

Bioinformatics analysis revealed that GAD1 and GAD2 were significantly upregulated in IA patients. GO enrichment analysis indicated that the biological processes involving DEGs primarily included the regulation of tumor necrosis factor production, negative regulation of cytokine production, T cell activation, and positive regulation of chemokine production. The main cellular components identified were the lysosomal membrane and neutrophil tertiary granules, while the molecular functions included cell adhesion cofactor activity. KEGG enrichment analysis demonstrated that the DEGs were predominantly involved in pathogenic Escherichia coli infection and the regulation of the actin cytoskeleton. qRT-PCR results showed that the expression levels of GAD1 and GAD2 in the peripheral blood of IA patients were significantly higher than those in the HC group (P < 0.05). ROC analysis revealed that the AUCs for GAD1 and GAD2 were 0.845 (95 % CI: 0.785-0.905) and 0.895 (95 % CI: 0.845-0.944), respectively. The levels of IL-6, IL-1β, and TNF-α in the peripheral blood of IA patients were significantly elevated compared to the HC group (P < 0.05). Pearson correlation analysis indicated that the levels of GAD1 and GAD2 were positively correlated with the levels of IL-6, IL-1β, and TNF-α (P < 0.05).

CONCLUSION

GAD1 and GAD2 are upregulated in the peripheral blood of IA patients and are positively correlated with the levels of IL-6, IL-1β, and TNF-α. These findings suggest that GAD1 and GAD2 may play a role similar to IL-6, IL-1β, and TNF-α in the pathogenesis of IA, potentially contributing to vascular wall damage, dilation, and rupture, thereby inducing IA formation.