Abstract
Background:
Accumulating evidence demonstrates that autophagy is important in inhibiting inflammation and cholesterol efflux. It suggested the autophagy may be a treatment of atherosclerosis. Thus, we screened autophagy-related mRNA to explore their mechanism of scientific basis for early diagnosis and therapy of atherosclerosis.
Methods:
The GSE28829 datasets were assessed to analyze differentially expressed genes by GEO2R. And autophagy-related hub genes were identified by HADb. The biological function of autophagy-related DEmRNAs was examined by Metascape. The construction of a protein-protein network was explored by String. Cytohubba was utilized to screen hub genes. Analysis of DEmiRNA-mRNA pairs was executed by DIANA microT-CDS database. Finally, correlation analysis was carried out to identify the relationship between DEARGs and clinical and prognostic factors.
Results:
A number of 1087 DEGs and 19 autophagy-related DEmRNAs were identified in advanced carotid atherosclerotic plaque compared with the early. The biological function containing development and growth was enriched. Moreover, we screened the top hub nodes with the highest degrees. MicroRNAs (miRNAs) are confirmed to participate in genesis and progression of atherosclerosis, so we further analyzed the miRNA-mRNA regulatory network genes with four hub genes to explore their potential mechanism in atherosclerosis. Then, we revealed co-expression of four key genes CTSB, ITGB1, CXCR4, TNFSF10 and autophagy-related genes. As for the clinical factors, hypertension factor showed higher expression of ITGB1. The probability of coronary heart disease factor was significantly increased with high expression of CTSB and CXCR4, as well as low expression of ITGB1 and TNFSF10. Diabetes factor tended to express distinguished levels of CTSB and ITGB1. TNFSF10 was highly expressed in both hyperlipidemia and ischemic stroke factor.
Conclusion:
CTSB, ITGB1, CXCR4 and TNFSF10 may be critical in atherosclerosis development and were thought to be potential diagnostic biomarkers for atherosclerosis.
Keywords:
atherosclerosis; autophagy; bioinformatics analysis; genes; miRNA.