Objective To identify and verify the key genes closely related to the vascular aging and progression of atherosclerosis(AS) through transcriptome sequencing and bioinformatics analysis.

Methods Four groups of mouse models were established, including the youth group(8-week-old C57BL/6J wild-type mice), natural aging group(22-month-old C57BL/6J wild-type mice), early AS group(early AS model constructed by 8-week-old ApoE-/- mice) and late AS group(late AS model constructed by 8-week-old ApoE-/- mice). The aortic tissues were taken for transcriptome sequencing analysis to screen the differential expressed genes(DEGs) related to vascular aging and AS progression, and the results were verified by reverse transcription polymerase chain reaction(RT-qPCR).

Results Taking the youth group as the control group, and the natural aging group as the experimental group, a total of 2,251 vascular aging-related DEGs were screened out. Taking the early AS group as the control group, and the advanced AS group as the experimental group, a total of 627 DEGs related to the progression of AS were screened out. Venn diagram analysis was conducted on the above two groups of DEGs, and 109 common core DEGs related to vascular aging and AS progression were screened out. Enrichment analysis revealed that the common core DEGs were significantly enriched in signaling pathways such as TNF and NF-κB. Protein-protein interaction(PPI) network analysis screened out a total of six Hub genes, namely Tyrobp, Ctss, Fcgr3, C1qa, C1qc and Fcer1g. RT-qPCR verification showed that the mRNA expression levels of the six Hub genes were upregulated in the natural aging group and advanced AS group(P ＜ 0.01), which was consistent with the results of transcriptome sequencing.

Conclusions Six key genes, including Tyrobp, are closely related to the vascular aging and progression of AS, and can serve as the potential biomarkers for vascular aging and progression of AS.