Comprehensive Analysis to Identify Key Genes Involved in Advanced Atherosclerosis.

BACKGROUND: The study was aimed at finding accurate and effective therapeutic targets and deepening our understanding of the mechanisms of advanced atherosclerosis (AA). METHODS: We downloaded the gene expression datasets GSE28829, GSE120521, and GSE43292 from Gene Expression Omnibus. Weighted gene coexpression network analysis (WGCNA) was performed for GSE28829, and functional enrichment analysis and protein-protein interaction network analysis were conducted on the key module. Significant genes in the key module were analyzed by molecular complex detection, and genes in the most important subnetwork were defined as hub genes. Multiple dataset analyses for hub genes were conducted. Genes that overlapped between hub genes and differentially expressed genes (DEGs) of GSE28829 and GSE120521 were defined as key genes. Further validation for key genes was performed using GSE28829 and GSE43292. Gene set enrichment analysis (GSEA) was applied to key genes. RESULTS: A total of 77 significant genes in the key module of GSE28829 were screened out that were mainly associated with inflammation and immunity. The subnetwork was obtained from significant genes, and 18 genes in this module were defined as hub genes, which were related to immunity and expressed in multiple diseases, particularly systemic lupus erythematosus. Some hub genes were regulated by SPI1 and associated with the blood, spleen, and lung. After overlapping with DEGs of GSE28829 and GSE120521, a total of 10 genes (HCK, ITGAM, CTSS, TYROBP, LAPTM5, FCER1G, ITGB2, NCF2, AIF1, and CD86) were identified as key genes. All key genes were validated and evaluated successfully and were related to immune response pathways. CONCLUSION: Our study suggests that the key genes related to immune and inflammatory responses are involved in the development of AA. This may deepen our understanding of the mechanisms of and provide valuable therapeutic targets for AA.

Local application of paeonol prevents early restenosis: a study with a rabbit vein graft model.

BACKGROUND: Neointimal hyperplasia, which is caused by dysfunction of vascular smooth muscle cells and vascular endothelial cells (VECs), is a foundation for later development of vein grafted occlusion. This study investigates whether neointimal hyperplasia could be prevented by the application of paeonol, a phenolic compound having functions of anti-inflammatory, anti-oxidant, and anti-proliferative. METHODS: Autologous jugular veins, which engrafted to carotid arteries in rabbits, were enveloped with paeonol or left untreated. After 0, 2, and 3 wk, vein grafts were respectively harvested. Proliferating cell nuclear antigen, vascular cell adhesion molecule l (VCAM-1), and intercellular cell adhesion molecule 1 were assessed with immunohistochemistry and Western blot. VECs apoptosis was also detected with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay. RESULTS: Paeonol treatment reduced early neointimal hyperplasia by 42%-46% (P < 0.001) and early medial hyperplasia by 18%-22% (P < 0.001) compared with the controls. Immunohistochemical and Western blot results show a significant downregulation of proliferating cell nuclear antigen (P < 0.001) and VCAM-1 (P < 0.001) in paeonol treatment group in the second and third weeks. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling analysis discovered that VECs apoptosis was also reduced by the paeonol treatment in the second and third weeks (P < 0.001). CONCLUSIONS: Paeonol could prevent vein graft early restenosis by suppressing intimal and medial hyperplasia via inhibition of vascular smooth muscle cells proliferation, VCAM-1 expression, and anti-apoptosis of VECs in grafted veins.