Analysis of immunogenic cell death in atherosclerosis based on scRNA-seq and bulk RNA-seq data

Abstract

Background: Regulated cell death plays a very important role in atherosclerosis (AS). Despite a large number of studies, there is a lack of literature on immunogenic cell death (ICD) in AS.

Method: Carotid atherosclerotic plaque single-cell RNA (scRNA) sequencing data were analyzed to define involved cells and determine their transcriptomic characteristics. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, CIBERSORT, ESTIMATE and ssGSEA (Gene Set Enrichment Analysis), consensus clustering analysis, random forest (RF), Decision Curve Analysis (DCA), and the Drug-Gene Interaction and DrugBank databases were applied for bulk sequencing data. All data were downloaded from Gene Expression Omnibus (GEO).

Result: mDCs and CTLs correlated obviously with AS occurrence and development (k²(mDCs) = 48.333, P < 0.001; k²(CTL) = 130.56, P < 0.001). In total, 21 differentially expressed genes were obtained for the bulk transcriptome; KEGG enrichment analysis results were similar to those for differentially expressed genes in endothelial cells. Eleven genes with a gene importance score > 1.5 were obtained in the training set and validated in the test set, resulting in 8 differentially expressed genes for ICD. A model to predict occurrence of AS and 56 drugs that may be used to treat AS were obtained with these 8 genes.

Conclusion: Immunogenic cell death occurs mainly in endothelial cells in AS. ICD maintains chronic inflammation in AS and plays a crucial role in its occurrence and development. ICD related genes may become drug-targeted genes for AS treatment.

Keywords: Immunogenic cell death (ICD); atherosclerosis (AS); bulk RNA sequencing; single-cell RNA sequencing.