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Updated: Nov 1, 2025
A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
Construction of a ceRNA immunoregulatory network related to the development of vascular dementia through a weighted
Hongshuo Shi1, Fengshan Sun2, Tiantian Yang3
1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Insights
Vascular dementia (VaD) lacks treatments, but this study identifies key immune factors and cell types, including lncRNA NEAT1, offering potential new therapeutic targets for VaD. This research provides novel immunologic insights for VaD treatment options.
Area of Science:
- Immunology
- Genomics
- Computational Biology
Background:
- Vascular dementia (VaD) currently lacks effective clinical treatments.
- Emerging evidence links VaD pathogenesis to immune system dysregulation.
- Competitive endogenous RNAs (ceRNAs) offer a novel avenue for studying VaD immunomodulation.
Purpose of the Study:
- To identify immune-related gene coexpression modules and construct a ceRNA network associated with VaD.
- To explore the role of immune cells and key molecular factors in VaD pathogenesis.
- To uncover potential therapeutic targets for VaD from an immunological perspective.
Main Methods:
- Weighted gene coexpression network analysis (WGCNA) and gene enrichment analysis on GEO database gene expression profiles.
- Construction of a lncRNA-miRNA-mRNA ceRNA network using Cytoscape.
- ImmuCellAI immune infiltration analysis and Gene Set Enrichment Analysis (GSEA).
Main Results:
- Identified a key immune-related module and constructed a VaD-associated ceRNA network.
- Natural killer T (NKT) cells implicated as key immune cells in VaD.
- Identified B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1 as potential key factors in VaD.
Conclusions:
- Novel therapeutic targets for VaD, including specific genes and lncRNA NEAT1, identified from an immunological standpoint.
- The study highlights the potential role of NKT cells and lncRNA NEAT1 regulation by NK cells and toll-like receptors in VaD.
- This research offers promising new treatment strategies for vascular dementia.
Background:
To date, vascular dementia (VaD) lacks effective treatment in clinical practice. There is also growing evidence that VaD may be closely related to the immune response. The development of high-throughput technology, and the recently discovered group of new mediators called competitive endogenous RNAs (ceRNA), provides a unique opportunity to study the immunomodulation of VaD.
Methods:
In this study, we used gene expression profiles in the Gene Expression Omnibus (GEO) database to obtain immune-related gene coexpression modules through a weighted gene coexpression network analysis (WGCNA) and gene enrichment analysis. We extracted and merged long non-coding RNA (lncRNA) and microRNA (miRNA) expressions from the GEO database and mapped them with related databases. Subsequently, we used Cytoscape to construct a lncRNA-miRNA-mRNA network, and then we performed an enrichment analysis on the mRNAs in the network to determine their regulatory function. Subsequently, we used an ImmuCellAI immune infiltration analysis and constructed a ceRNA sub-network of related immune cells. Finally, we conducted a gene set enrichment analysis (GSEA) to determine the potential regulatory pathways of the key factors.
Results:
As a result, we identified the blue module as the key module of immunity and constructed the related CeRNA network. Immune infiltration analysis showed that natural killer T (NKT) cells may be the key immune cells of VaD. Using a Pearson correlation analysis, we identified that B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1 may be the key factors of VaD. Our subsequent GSEA analysis showed that lncRNA NEAT1 may be regulated by NK cells and toll-like receptors.
Conclusions:
Our research provides new therapeutic targets for vascular dementia from the immunological perspective for the first time, including B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1, and our research hopes to provide new treatment options for VaD.
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