The Identification of Candidate Biomarkers and Pathways in Atherosclerosis by Integrated Bioinformatics Analysis

Abstract

Background. Atherosclerosis (AS) is a type of yellow substance containing cholesterol in the intima of large and middle arteries, which is mostly caused by fat metabolism disorders and neurovascular dysfunction. Materials and Methods. The GSE100927 data got analyzed to find out the differentially expressed genes (DEGs) using the limma package in R software. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the DEGs were assessed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The Search Tool for the Retrieval of Interacting Genes (STRING) visualized the Protein-Protein Interaction (PPI) network of the aggregated DEGs. GSEA software was used to verify the biological process. Result. We screened 1574 DEGs from 69 groups of atherosclerotic carotid artery and 35 groups of control carotid artery, including 1033 upregulated DEGs and 541 downregulated DEGs. DEGs of AS were chiefly related to immune response, Epstein-Barr virus infection, vascular smooth muscle contraction, and cGMP-PKG signaling pathway. Through PPI networks, we found that the hub genes of AS were PTAFR, VAMP8, RNF19A, VPRBP, RNF217, KLHL42, NEDD4, SH3RF1, UBE2N, PJA2, RNF115, ITCH, SKP1, FBXW4, and UBE2H. GSEA analysis showed that GSE100927 was concentrated in RIPK1-mediated regulated necrosis, FC epsilon receptor fceri signaling, Fceri-mediated NF KB activation, TBC rabgaps, TRAF6-mediated induction of TAK1 complex within TLR4 complex, and RAB regulation of trafficking. Conclusion. Our analysis reveals that immune response, Epstein-Barr virus infection, and so on were major signatures of AS. PTAFR, VAMP8, VPRBP, RNF217, KLHL42, and NEDD4 might facilitate the AS tumorigenesis, which could be new biomarkers for diagnosis and therapy of AS.

Turning Hot into Cold: Immune Microenvironment Reshaping for Atherosclerosis Attenuation Based on pH-Responsive shSiglec-1 Delivery System

“…As shown in the top half of the graph, pathways related to AMPK signaling and ABC transporters were significantly upregulated, which most likely contributed to cholesterol efflux by PEI-ASA. In addition, a pathway related to autophagy, which can inhibit the development of atherosclerosis, was also found to be significantly upregulated. , Moreover, some DEGs enriched pathways were reported to have a close relationship with atherosclerosis, containing an oxytocin-signaling pathway, proteoglycans in cancer, cGMP-PKG signaling pathway, regulation of actin cytoskeleton, and synthesis and degradation of ketone bodies . Furthermore, in the bottom half of the graph (Figure E), signaling pathways related to nonalcoholic fatty liver disease and insulin resistance were markedly downregulated, which can be attributed to the antihyperlipidemic effects of PEI-ASA.…”

“…40,41 Moreover, some DEGs enriched pathways were reported to have a close relationship with atherosclerosis, containing an oxytocin-signaling pathway, proteoglycans in cancer, cGMP-PKG signaling pathway, regulation of actin cytoskeleton, and synthesis and degradation of ketone bodies. 42 Furthermore, in the bottom half of the graph (Figure 8E), signaling pathways related to nonalcoholic fatty liver disease and insulin resistance were markedly downregulated, which can be attributed to the antihyperlipidemic effects of PEI-ASA. In addition, many signaling pathways related to the atherosclerosis-related disease database were also found significantly downregulated, containing Cushing's syndrome, breast cancer, endocytosis, Alzheimer's disease, and fat digestion and absorption.…”

Proteomics-based evaluation of the mechanism underlying vascular injury via DNA interstrand crosslinks, glutathione perturbation, mitogen-activated protein kinase, and Wnt and ErbB signaling pathways induced by crotonaldehyde

“…The expression of a protein (FC = 1.65), such as breast cancer anti-estrogen resistance 1 (protein accession number Q96CD4), is associated with elevated vascular endothelial growth factor and p53 expression levels [ 67 ]. Upon treatment with CRA, upregulation of RNF115 genes, followed by expression of E3 ubiquitin-protein ligase RNF115 (FC = 16.09) with protein accession number Q9Y4L5, was found to be linked to atherosclerosis pathways [ 68 ].…”

Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions

“…FER regulated cell–cell adhesion and absence of FER protein tyrosine kinase could induce epithelial barrier dysfunction [ 55 ] which was regarded as a hallmark of many human panvascular diseases, including atherosclerosis, hypertension and diabetes [ 56 ]. One study demonstrated the association of PJA2 with atherosclerosis through protein–protein interaction network analysis [ 57 ]. The unweighted and weighted GRSs were significantly associated with SCA among PWH under 45 years old, which might be used as the predictive biomarker panel of SCA among young HIV-infected adults.…”