Identification of Hub Genes Associated with Abnormal Endothelial Function in Early Coronary Atherosclerosis

Abnormal coronary endothelial function is an important step in the development of atherosclerosis. Coronary atherosclerosis is one of the main causes of death worldwide. We constructed a co-expression network to identify hub genes associated with abnormal coronary endothelial function in early coronary atherosclerosis. In brief, we used the GSE132651 dataset from the gene expression omnibus database. The top 5000 genes with greatest variances were used for weighted gene co-expression network analysis, and the module most strongly correlated with abnormal coronary endothelial function was chosen as key module. Functional enrichment analysis was performed for genes in the key module, a protein-protein interaction network was constructed to find hub genes, and gene set enrichment analysis (GSEA) was also performed. Genes were classified into 7 modules, with the midnightblue module being the one that was most related to abnormal coronary endothelial function and containing genes enriched in DNA replication, cell cycle, nucleotide excision repair, and Human T-cell leukemia virus 1 infection. We identified nine hub genes (HOXC5, PRND, PADI3, RC3H1, DAPP1, SIT1, DRICH1, GPRIN2, and RHO), which differently expressed in abnormal and normal coronary endothelial function samples. GSEA suggested that samples associated with abnormal coronary endothelial function and highly expressed hub genes were linked with immune, coagulation, hypoxia, and angiogenesis processes. These hub genes, their expression pattern, and pathways may be involved in the development of abnormal coronary endothelial function and promotion of early coronary atherosclerosis.