Hypercholesterolemia induces vascular immune responses to accelerate atherosclerosis progression in high fat diet-fed Tibetan minipigs

We used transcriptomics to identify vascular gene expression profiles of high-fat-fed Tibetan minipig induced-hypercholesterolemia and atherosclerotic models, to verify the hypothesis that hypercholesterolemia induces innate and adaptive immune responses to accelerate atherosclerosis. Results showed that hypercholesterolemia and atherosclerosis models occurred in the high-fat fed minipigs at 8 and 24 weeks. GSEA analysis showed that the changes of hypercholesterolemia accelerated atherosclerosis were focused on immunity inflammation and lipid metabolism, immune cells such as NK cells and T cells participated in the biological processes. 4 significant modules of 344 overlapping DEGs were identified by STEM analysis. 6 hub genes (ITGB2, TYROBP, LCP2, PTPRC, C5AR1, and PTPN6) and two immune-related pathways (Natural killer cell-mediated cytotoxicity and T cell receptor signaling pathway) were identified by CytoHubba plugin and KEGG analysis. Correlation analysis showed that hub genes were significantly correlated with lipid deposition, IMT, WBC, CD4, and CD8, which was consistent with RT-PCR validation results. From above, this study reveals that hypercholesterolemia accelerate atherosclerosis progression by inducing innate and adaptive immune responses. Examination of the changes of vascular gene expression profiles in hypercholesterolemia and atherosclerosis models induced by high-fat diet in Tibetan minipigs and compared with normal control group