Analysis of genes and underlying mechanisms involved in foam cells formation and atherosclerosis development

Abstract

Background Foam cells (FCs) play crucial roles in the process of all stages of atherosclerosis. Smooth muscle cells (SMCs) and macrophages are the major sources of FCs. This study aimed to identify the common molecular mechanism in these two types of FCs. Methods GSE28829, GSE43292, GSE68021, and GSE54666 were included to identify the differentially expressed genes (DEGs) associated with FCs derived from SMCs and macrophages. Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using the DAVID database. The co-regulated genes associated with the two origins of FCs were validated (GSE9874), and their expression in vulnerable atherosclerosis plaques (GSE120521 and GSE41571) was assessed. Results A total of 432 genes associated with FCs derived from SMCs (SMC-FCs) and 81 genes associated with FCs derived from macrophages (M-FCs) were identified, and they were mainly involved in lipid metabolism, inflammation, cell cycle/apoptosis. Furthermore, three co-regulated genes associated with FCs were identified: GLRX, RNF13, and ABCA1. These three common genes showed an increased tendency in unstable or ruptured plaques, although in some cases, no statistically significant difference was found. Conclusions DEGs related to FCs derived from SMCs and macrophages have contributed to the understanding of the molecular mechanism underlying the formation of FCs and atherosclerosis. GLRX, RNF13, and ABCA1 might be potential targets for atherosclerosis treatment.

RNF13 Dileucine Motif Variants L311S and L312P Interfere with Endosomal Localization and AP-3 Complex Association

“…RNF13 plays a role in myogenesis, tumorigenesis, and cell proliferation [29,32,33]. Recent studies have shown that RNF13 expression in atherosclerosis plaques is upregulated [34], while it is downregulated in uveal melanoma [35] and asthma [36]. Ectopic expression of RNF13 inhibits myoblast proliferation, whereas treatment with myostatin, a muscle growth inhibitor, upregulates RNF13 expression [32].…”

Mettl3 promotes oxLDL‐mediated inflammation through activating STAT1 signaling

“… 6 , 7 In plaque microenvironment, low‐density lipoprotein is not only phagocytized by macrophages to induce the formation of foam cells but also stimulates macrophages to release inflammatory factors such as interleukin‐6 (IL‐6) and tumor necrosis factor alpha (TNF‐α). 8 , 9 , 10 Recent studies revealed that signal transducer and activator of transcription 1 (STAT1), a novel therapeutical target for AS, act crucial roles in the pathology of AS through promoting expressions of several pro‐inflammatory and pro‐atherogenic mediators in macrophages. 11 Targeted inhibition of STATs and IRFs was reported to be a potential treatment strategy in cardiovascular disease.…”

Bioinformatic Analysis Revealed the Essential Regulatory Genes and Pathways of Early and Advanced Atherosclerotic Plaque in Humans

“…Previous studies have used the microarray datasets of GSE43292 and GSE28829 to screen DEGs, key genes, and pathways in a single atherosclerotic plaque stage [ 17 , 18 , 31 , 32 , 33 ]. In comparison, the current study comprehensively investigated the gene expression profiles of atherosclerotic plaque in the stages of non-plaque to plaque as well as early to advanced.…”