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Endothelial cell dysfunction plays a major role in the pathogenesis of atherosclerosis. However, it is currently unclear which genes are involved between endothelial cell dysfunction and atherosclerosis. This study was aimed at identifying these genes. Based on the GSE83500 dataset, the quantification of endothelial cell function was conducted using single\u2010sample gene set enrichment analysis; the coexpression modules were conducted using weighted correlation network analysis. After building module\u2010trait relationships, tan and yellow modules were regarded as hub modules. 10 hub genes from each hub module were identified by the protein\u2010protein interaction network analysis. The key genes (<jats:italic>RAB5A<\/jats:italic>, <jats:italic>CTTN<\/jats:italic>, <jats:italic>ITGB1<\/jats:italic>, and <jats:italic>MMP9<\/jats:italic>) were obtained by comparing the expression differences of the hub gene between atherosclerotic and normal groups from the GSE28829 and GSE43292 datasets, respectively. ROC analysis showed the diagnostic value of key genes. Moreover, the differential expression of key genes in normal and atherosclerotic aortic walls was verified. <jats:italic>In vitro<\/jats:italic>, we establish a model of ox\u2010LDL\u2010injured endothelial cells and transfect <jats:italic>RAB5A<\/jats:italic> overexpression and shRNA plasmids. The results showed that overexpression of <jats:italic>RAB5A<\/jats:italic> ameliorates the proliferation and migration function of ox\u2010LDL\u2010injured endothelial cells, including the ability of tubule formation. It was speculated that the interferon response, Notch signaling pathways, etc. were involved in this function of <jats:italic>RAB5A<\/jats:italic> by using gene set variation analysis. With the multiple bioinformatics analysis methods, we detected that yellow and tan modules are related to the abnormal proliferation and migration of endothelial cells associated with atherosclerosis. <jats:italic>RAB5A<\/jats:italic>, <jats:italic>CTTN<\/jats:italic>, <jats:italic>ITGB1<\/jats:italic>, and <jats:italic>MMP9<\/jats:italic> can be used as potential targets for therapy and diagnostic markers. <jats:italic>In vitro<\/jats:italic>, overexpression of <jats:italic>RAB5A<\/jats:italic> can ameliorate the proliferation and migration function of ox\u2010LDL\u2010injured endothelial cells, and the possible molecules involved in this process were speculated.<\/jats:p>","DOI":"10.1155\/2022\/5544276","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T23:35:06Z","timestamp":1641857706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Key Genes Associated 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