Identification of Potential Ferroptosis-Related Genes in Human Carotid Atherosclerosis

Abstract Background: Carotid atherosclerosis (CAS) is a common chronic vascular inflammatory disease and one of the main causes of cardiovascular and cerebrovascular diseases (CVDs). Ferroptosis-related genes (FRGs) may play a crucial part in pathophysiological processes of CAS. However, the expression profile of FRGs have rarely been adopted to explore the relationship between ferroptosis and CAS. Objects: Therefore, using the expression profile of FRGs to explore the relationship between ferroptosis and CAS may provide new insights for the prevention and treatment of CVD. Methods: The differentially expressed genes (DEGs) of the GSE432192 dataset were obtained from the Gene Expression Omnibus (GEO) database. Ferroptosis-related-genes (FRGs) were identified by downloading data from the FerrDb database. The GSE432192 dataset contains 32 carotid atheroma plaque samples and 32 macroscopically intact carotid tissue samples adjacent to the atheroma plaque. The differentially expressed FRGs (DE-FRGs) of the GSE432192 dataset were screened and analyzed by gene ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes analysis (KEGG), protein-protein interaction network (PPI), and were chosen to explore related miRNAs. Results: The GSE432192 dataset had a total of 41 DE-FRGs. The GO analysis results revealed that DE-FRGs were mainly enriched in response to oxidative stress, oxidoreductase activity acting on NAD(P)H, and apical part of cell. KEGG analysis results showed that DE-FRGs were mainly enriched in ferroptosis and chemical carcinogenesis – reactive oxygen species relating pathways. Expressions of top 5 hub genes, as HIF1A, HMOX1, TFRC, CYBB, EGFR, were regarded as focus in the PPI regulatory networks. Conclusions: In this study, Ferroptosis and FRGs may play a vital role in regulating the pathophysiology of CAS.