Abstract： Objective To analyze and validate the potential molecular mechanisms involved in the formation of vulnerable atherosclerosis plaques through the miRNA-mRNA regulatory network.Methods Morphological staining was used to validate the presence of atherosclerotic plaques in the aortic root and brachiocephalic trunk.Differentially ex-pressed miRNAs(DEMs)from the GSE34646 and GSE34647 datasets were analyzed,and their target genes(DEMs-TGs)were predicted.Differentially expressed genes in advanced plaque(DEGs-AP)were then screened from the GSE10000 dataset.The intersection of DEGs-AP and DEMs-TGs was taken to identify candidate genes.A protein-protein interaction(PPI)network was constructed for the identified genes,and key genes were identified.An miRNA-mRNA regulatory network was established,and the prognostic value of key genes was assessed using receiver operating characteristic(ROC)curves.Finally,RT-qPCR was used to detect the predicted mRNA and miRNA levels in the aorta.Results Histopathological examination showed significant vulnerable plaques in the model group.Forty-four DEMs were identified in vulnerable plaques from the GSE34646 and GSE34647 datasets,predicting 3,171 and 8,075 miRNA target genes,respectively.The GSE10000 dataset identified 3,441 DEGs-AP.The intersection of DEGs-AP and DEMs-TGs yielded 936 candidate genes.The PPI network identified 10 upregulated and 10 downregulated hub genes,which were used to construct the miRNA-mRNA regulatory network.Conclusion Let-7g-3p-ADAM10/PIK3R1/C3AR1 may be the potential miRNA-mRNA regulatory axes for prognostication and diagnosis of advanced plaques by the RT-qPCR.