Identification of key signaling pathways in cerebral small vessel disease using differential pathway network analysis

Cerebral small vessel disease (CSVD) primarily affects the perforating cerebral arterioles and capillaries, and results in injury to subcortical grey and white matter. Despite advances in determining the genetic basis of CSVD, the molecular mechanisms underlying the development and progression of CSVD remain unclear. The present study aimed to identify significant signaling pathways associated with CSVD based on differential pathway network analysis. Combining CSVD microarray data with human protein-protein interaction data and data from the Reactome pathway database, pathway interactions were constructed using the Spearman's correlation coefficient strategy. Pathway interactions with weight values of >0.95 were selected to construct the differential pathway network, which contained 715 differential pathway interactions covering 312 nodes and was visualized using Cytoscape software. A total of 15 hub pathways with a top 5% degree distribution in the differential pathway network were identified. The top 5 hub pathways were associated with the synthesis and metabolism of fatty acids. The results of the present study indicate that the synthesis and metabolism of fatty acids is associated with the occurrence and development of CSVD, and may thus provide insights to improve the early diagnosis and treatment of CSVD.