ArticleJournal of neuroinflammation2024
Multiomics integrated analysis and experimental validation identify TLR4 and ALOX5 as oxidative stress-related biomarkers in intracranial aneurysms.
Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- Intracranial aneurysms as a manifestation of premature vascular aging: Cellular senescence, inflammaging, and wall degeneration.Ageing research reviews · 2026Review
- Integrative gene target mapping, RNA sequencing, in silico molecular docking, ADMET profiling and molecular dynamics simulation study of marine derived molecules for type 1 diabetes mellitus.Molecular diversity · 2026Article
- LDHA protects vascular endothelial cells from oxidative stress‑induced mitochondrial damage via HIF‑1α activation and glycolytic reprogramming.Molecular medicine reports · 2026Article
- Novel VSMC-associated biomarkers in intracranial aneurysm pathogenesis: a multi-omics and machine learning study.BMC neurology · 2026Article
- Secretory VSMC-derived THBS1 promotes macrophage M1 polarization and inflammation in intracranial aneurysms via the CD47/NF-κB axis.Frontiers in immunology · 2026Article
- Circulating proteins as key genetically proxied mediators in the pathway from smoking to intracranial aneurysm disease: A mediation Mendelian randomization analysis.Tobacco induced diseases · 2026Article
- Potential drug targets for intracranial aneurysms identified through Mendelian randomization analysis.Neurosurgical review · 2025Article
- LncRNA PVT1 Facilitates Phenotypic Switching of Vascular Smooth Muscle Cells in Intracranial Aneurysms by Recruiting KDM1A to Reduce H3K9me2 Modification.The Kaohsiung journal of medical sciences · 2025Article
- Identification of key therapeutic targets in nicotine-induced intracranial aneurysm through integrated bioinformatics and machine learning approaches.BMC pharmacology & toxicology · 2025Article
- Intracranial Aneurysm Biomarkers: A Convergence of Genetics, Inflammation, Oxidative Stress, and the Extracellular Matrix.International journal of molecular sciences · 2025Review
- Integrative Analysis and Experimental Validation Reveal FCGR1A and ITGAL as Key Inflammatory Biomarkers in Proliferative Diabetic Retinopathy.Journal of inflammation research · 2025Article
- Exploration of Immune-Related Transcription Control/Regulation in Intracranial Aneurysm Through KEGG Analysis and in-vivo Validation.Journal of inflammation research · 2025Article
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14 authors.
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Abstract
backgroundIntracranial aneurysm (IA) is a severe cerebrovascular disease, and effective gene therapy and drug interventions for its treatment are still lacking. Oxidative stress (OS) is closely associated with the IA, but the key regulatory genes involved are still unclear. Through multiomics analysis and experimental validation, we identified two diagnostic markers for IA associated with OS.
methodsIn this study, we first analyzed the IA dataset GSE75436 and conducted a joint analysis of oxidative stress-related genes (ORGs). Differential analysis, functional enrichment analysis, immune infiltration, WGCNA, PPI, LASSO, and other methods were used to identify IA diagnostic markers related to OS. Next, the functions of TLR4 and ALOX5 expression in IA and their potential targeted therapeutic drugs were analyzed. We also performed single-cell sequencing of patient IA and control (superficial temporal artery, STA) tissues. 23,342 cells were captured from 2 IA and 3 STA samples obtained from our center. Cell clustering and annotation were conducted using R software to observe the distribution of TLR4 and ALOX5 expression in IAs. Finally, the expression of TLR4 and ALOX5 were validated in IA patients and in an elastase-induced mouse IA model using experiments such as WB and immunofluorescence.
resultsThrough bioinformatics analysis, we identified 16 key ORGs associated with IA pathogenesis. Further screening revealed that ALOX5 and TLR4 were highly expressed to activate a series of inflammatory responses and reduce the production of myocytes. Methotrexate (MTX) may be a potential targeted drug. Single-cell analysis revealed a notable increase in immune cells in the IA group, with ALOX5 and TLR4 primarily localized to monocytes/macrophages. Validation through patient samples and mouse models confirmed high expression of ALOX5 and TLR4 in IAs.
conclusionsBioinformatics analysis indicated that ALOX5 and TLR4 are the most significant ORGs associated with the pathogenesis of IA. Single-cell sequencing and experiments revealed that the high expression of ALOX5 and TLR4 are closely related to IA. These two genes are promising new targets for IA therapy.
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