Identification of core genes associated with the anti-atherosclerotic effects of Salvianolic acid B and immune cell infiltration characteristics using bioinformatics analysis

Background: ： Atherosclerosis (AS) is the greatest contributor to pathogenesis of atherosclerotic cardiovascular disease (ASCVD), which is associated with increased mortality and reduced quality of life. Early intervention to mitigate AS is key to prevention of ASCVD. Salvianolic acid B (Sal B) is mainly extracted from root and rhizome of Salvia Miltiorrhiza Bunge , and exerts anti-atherosclerotic effect. The purpose of this study was to screen for anti-AS targets of Sal B and to characterize immune cell infiltration in AS. Methods: ： We identified targets of Sal B using SEA (http://sea.bkslab.org/) and SIB (https://www.sib.swiss/) databases. GSE2289 dataset was obtained from Gene Expression Omnibus database. We identified differentially expressed genes (DEGs) and performed KEGG analysis, GO analysis with Metascape (https://metascape.org/databae). Weighted gene co-expression network analysis (WGCNA) was used to determine the most relevant module associated with atherosclerotic plaque stability. Intersecting candidate genes were evaluated by generating receiver operating characteristic (ROC) curves, and molecular docking was performed. Finally, immune cell types were identified using CIBERSOFT, the relationship between candidate genes and immune cell infiltration was evaluated. Results: ： MMP9 and MMP12 were been selected as candidate genes from 171 DEGs and turquoise module with 370 genes.ROC curve results showed that MMP9 (AUC=0.899, p=0.00013) and MMP12 (AUC=0.880, p=0.00038) were positively associated with advanced atherosclerotic plaques, and Sal B bound strongly to MMP9 and MMP12. The results of immune cell infiltration showed that naive B cells, memory B cells, regulatory T cells, gamma delta T cells, M0 macrophages, M2 macrophages, activated dendritic cells, and resting mast cells may be involved in development of AS, and the candidate genes MMP9 and MMP12 were associated with these immune cells to different degrees. Conclusion: ： The anti-AS effects of Sal B may be related to MMP9 and MMP12 and associated with immune cell infiltration,which is expected to be used in the early intervention of AS.