Abstract
Intracranial aneurysms (IAs) may cause lethal subarachnoid hemorrhage upon rupture, but the molecular mechanisms are poorly understood. The aims of this study were to analyze the transcriptional profiles to explore the functions and regulatory networks of differentially expressed genes (DEGs) in IA rupture by bioinformatics methods and to identify the underlying mechanisms. In this study, 1,471 DEGs were obtained, of which 619 were upregulated and 852 were downregulated. Gene enrichment analysis showed that the DEGs were mainly enriched in the inflammatory response, immune response, neutrophil chemotaxis, and macrophage differentiation. Related pathways include the regulation of actin cytoskeleton, leukocyte transendothelial migration, nuclear factor κB signaling pathway, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, and chemokine signaling pathway. The enrichment analysis of 20 hub genes, subnetworks, and significant enrichment modules of weighted gene coexpression network analysis showed that the inflammatory response and immune response had a causal relationship with the rupture of unruptured IAs (UIAs). Next, the CIBERSORT method was used to analyze immune cell infiltration into ruptured IAs (RIAs) and UIAs. Macrophage infiltration into RIAs increased significantly compared with that into UIAs. The result of principal component analysis revealed that there was a difference between RIAs and UIAs in immune cell infiltration. A 4-gene immune-related risk model for IA rupture (IRMIR), containing CXCR4, CXCL3, CX3CL1, and CXCL16, was established using the glmnet package in R software. The receiver operating characteristic value revealed that the model represented an excellent clinical situation for potential application. Enzyme-linked immunosorbent assay was performed and showed that the concentrations of CXCR4 and CXCL3 in serum from RIA patients were significantly higher than those in serum from UIA patients. Finally, a competing endogenous RNA network was constructed to provide a potential explanation for the mechanism of immune cell infiltration into IAs. Our findings highlighted the importance of immune cell infiltration into RIAs, providing a direction for further research.
Highlights
Intracranial aneurysms (IAs) are abnormal bumps that occur in an arterial wall, and they are an important cause of spontaneous subarachnoid hemorrhage (SAH) (Macdonald and Schweizer, 2017)
We found that the inflammatory response and immune cell infiltration had a causal relationship with the rupture of unruptured IAs (UIAs)
Enzyme-linked immunosorbent assay (ELISA) showed that the CXCR4 and CXCL3 concentrations in the serum from ruptured IAs (RIAs) patients were significantly higher than those in the serum from UIA patients
Summary
Intracranial aneurysms (IAs) are abnormal bumps that occur in an arterial wall, and they are an important cause of spontaneous subarachnoid hemorrhage (SAH) (Macdonald and Schweizer, 2017). The molecular mechanisms of the formation and rupture of IAs remain unclear. With the rapid development of microarray technology, the GEO database has gradually played an important role in bioinformatics analysis (Zhang et al, 2019). Inflammation and immune cell infiltration, including macrophages, mast cells (Furukawa et al, 2020), and monocytes, play important roles in the formation and rupture of IAs. A previous study confirmed that inflammationaccelerated Toll-like receptor 4 (TLR4) pathway in aneurysmal walls promoted the development of IA rupture (Mitsui et al, 2020). Kanematsu et al (2011) reported that the infiltration and polarization of macrophages were closely related to the rupture of IAs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
