Identification of Candidate Genes Associated with Development of Vascular Cognitive Impairment by Integrated Bioinformatics Analysis Combined with Biological Experiments

Abstract

Abstract The morbidity and mortality associated with vascular cognitive impairment (VCI) generally increase steeply, and health systems will face increasing demand for services. The present study aims to screen key genes to give new insight into the mechanisms and treatment of VCI based on bioinformatic approaches combined with biological experiments in rats. The gene expression data of VCI patients contained in the GSE122063 dataset were downloaded from the GEO. We performed a weighted gene co-expression network analysis (WGCNA) to identify a hub module and 44 hub genes.277 differentially expressed genes (DEGs) were analyzed using R software by the “limma” package. STRING database was used to construct protein-protein interaction (PPI) network, after which 36 hub genes were identified through Cytoscape. Functional enrichment analysis revealed that these genes from the yellow module and 277 DEGs were mainly associated with these pathways, such as staphylococcus aureus infection, complement, and coagulation cascades. These biological functions are related to inflammatory cell activation and inflammatory response. The key genes of VCI were the overlapping hub genes from the yellow module and the PPI network. The expressions of hub genes in rats were determined by qRT-PCR, western blot, immunohistochemistry, and immunofluorescence. In conclusion, C1QA, C1QB, C1QC, CD163, and FCGR2A were highly expressed in the hippocampus of VCI rats, and they can serve as candidate biomarkers for the diagnosis and prognosis of VCI. Finally, molecular docking results suggested that five genes interact with Bisphenol A. These findings open a new avenue to investigate molecular mechanisms for preventing or treating vascular cognitive impairment.