ORIGINAL RESEARCH article
Front. Genet.
Sec. Human and Medical Genomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1646991
Comprehensive analysis and validation of angiogenesis in vascular dementia from the perspective of diagnosis, prevention, and treatment
Provisionally accepted
- 1Anhui University of Chinese Medicine, Hefei, China
- 2Hefei High-tech Cardiovascular Hospital, hefei, China
- 3The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
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Background: Angiogenesis is a critical pathological process in vascular dementia (VD), yet current therapeutic strategies targeting this mechanism remain limited. Identifying novel molecular pathways involved in angiogenesis holds significant promise for advancing both diagnostic and therapeutic approaches for VD. Methods: We first applied weighted gene coexpression network analysis (WGCNA) and differentially expressed gene (DEG) analysis, combined with phenotypic gene database mining, to identify angiogenesis-associated genes in VD. We then used the Least Absolute Shrinkage and Selection Operator (LASSO) regression to select key diagnostic genes. The diagnostic efficacy of these genes was evaluated using receiver operating characteristic (ROC) curve analysis, while their association with immune cell infiltration was assessed via xCell immunoinfiltration. Using single-nucleus RNA sequencing (snRNA-seq), we determined the cellular distribution of key genes and applied Gene Set Enrichment Analysis (GSEA) to analyze functional pathways in the differentially expressed cell clusters. Finally, we validated gene expression changes in the hippocampus of bilateral common carotid artery occlusion (BCCAO)-induced VD rats using quantitative polymerase chain reaction (qPCR) and western blot (WB). Results: Ultimately, we screened five key genes, namely CCL2, VEGFA, SPP1, ANGPT2, and ANGPTL4, which were all down-regulated in the BCCAO model. The results of snRNA-seq showed that key genes were mainly clustered in microglia, endothelial cells, and astrocytes. Microglia, endothelial cells, and astrocytes play a key role in regulating angiogenesis. Conclusion: These five key genes might be used as angiogenesis diagnostic genes for VD and might be novel potential targets for diagnosis, treatment, and prevention.
Keywords: Vascular Dementia, Angiogenesis, bioinformatics, snRNA-seq analysis, experimental verification
Received: 14 Jun 2025; Accepted: 19 Aug 2025.
Copyright: © 2025 Wang, Xu and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: YuJiao Wang, Anhui University of Chinese Medicine, Hefei, China
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