Identifying potential cross‐talk signatures for the occurrence of atherosclerosis in diabetic erectile dysfunction

Abstract Background Erectile dysfunction and atherosclerosis are common cardiovascular complications in diseases. Clinical associations between erectile dysfunction and atherosclerosis have been noticed, but the specific mechanisms are not illustrated adequately. Objectives The aim of the study was to further mine associated pathological mechanisms and genetic alterations of atherosclerosis in diabetes mellitus‐related erectile dysfunction. Materials and methods Significant atherosclerosis‐related genes were identified from transcriptome data of diabetes mellitus‐related erectile dysfunction and atherosclerosis‐related gene sets from DisGeNET and GeneCard databases. Functional enrichment and immune infiltration analyses were performed to clarify the biological roles and pathways as well as immune responses of significant atherosclerosis‐related gene sets. A protein–protein interaction network was constructed, and gene clusters were performed. Then, data of diabetic plaques and high‐glucose cavernosum endothelial cells were analyzed for validation. And hub atherosclerosis‐related gene sets were identified. Finally, expressed pattern of hub atherosclerosis‐related gene sets were explored by single‐cell profiling and immune analysis. Results In total, 202 significant atherosclerosis‐related gene sets including 100 upregulated and 102 downregulated genes were identified. These genes were related to endothelial cell migration, inflammatory response, regulation of oxidative stress, and immune response. In immune infiltration, immature dendritic cells and monocytes showed differential expression between the diabetes mellitus‐related erectile dysfunction and control groups, A protein–protein interaction network containing 135 nodes was constructed. A hub atherosclerosis‐related gene set signature consisting of HBEGF, LOX, NQO1, and VLDLR was obtained by multi‐omics validation. In addition, Functional enrichment analysis revealed that hub atherosclerosis‐related gene sets were involved in oxidoreductase activity and extracellular matrix organization. Discussion and conclusion We explored atherosclerosis‐related genetic changes and signaling pathways in diabetes mellitus‐related erectile dysfunction. HBEGF, LOX, NQO1, and VLDLR were identified as hub atherosclerosis‐related gene sets. These may serve as potential biomarkers for the clinical management of atherosclerosis and preventing further cardiovascular risks in diabetes mellitus‐related erectile dysfunction.