Identification of Crucial Genes and Pathways Associated with Atherosclerotic Plaque in Diabetic Patients

Abstract

Background Patients with diabetes have more calcification in atherosclerotic plaque and a higher occurrence of secondary cardiovascular events than patients without diabetes. The objective of this study was to identify crucial genes involved in the development of diabetic atherosclerotic plaque using a bioinformatics approach. Methods Microarray dataset GSE118481 was downloaded from the Gene Expression Omnibus (GEO) database; the dataset included 6 patients with diabetic atherosclerotic plaque (DBT) and 6 nondiabetic patients with atherosclerotic plaque (Ctrl). Differentially expressed genes (DEG) between the DBT and Ctrl groups were identified and then subjected to functional enrichment analysis. Based on the enriched pathways of DEGs, diabetic atherosclerotic plaque-related pathways were screened using the comparative toxicogenomics database (CTD). We then constructed a protein–protein interaction (PPI) network and transcription factor (TF)–miRNA–mRNA network. Results A total of 243 DEGs were obtained in the DBT group compared with the Ctrl group, including 85 up-regulated and 158 down-regulated DEGs. Functional enrichment analysis showed that up-regulated DEGs were mainly enriched in isoprenoid metabolic process, DNA-binding TF activity, and response to virus. Additionally, DEGs participating in the toll-like receptor signaling pathway were closely related to diabetes, carotid stenosis, and insulin resistance. The TF–miRNA–mRNA network showed that toll-like receptor 4 ( TLR4 ), BCL2-like 11 ( BCL2L11 ), and glutamate-cysteine ligase catalytic subunit ( GCLC ) were hub genes. Furthermore, TLR4 was regulated by TF signal transducer and activator of transcription 6 (STAT6); BCL2L11 was targeted by hsa-miR-24-3p; and GCLC was regulated by nuclear factor, erythroid 2 like 2 (NFE2L2). Conclusion Identification of hub genes and pathways increased our understanding of the molecular mechanisms underlying the atherosclerotic plaque in patients with or without diabetes. These crucial genes ( TLR4, BC2L11 , and GCLC ) might function as molecular biomarkers for diabetic atherosclerotic plaque.

Identification of potential biomarkers and pathways associated with carotid atherosclerotic plaques in type 2 diabetes mellitus: A transcriptomics study

“…Unfortunately, plaque stability cannot be determined histologically despite the increasing number of methods to detect the development of CAPs in T2DM patients. Earlier bioinformatics studies have reported that T2DM alters CAP gene expression (13), but this has not been further confirmed with transcriptomics. Consequently, key biomarkers for T2DM complicated by CAP progression are currently unavailable.…”

“…Previous studies have assessed the role of RNAs that are associated with T2DM and CAP progression (75,76). However, only a few studies (13), including this study, have explored the progression of T2DM with CAP using advanced bioinformatic methods. While our results provide useful insights into the role of certain genes and RNAs in the progression of T2DM with CAP, our study also has a few limitations.…”

Construction of an HCC recurrence model based on the investigation of immune-related lncRNAs and related mechanisms

“… 34 , 35 However, the mechanism behind lncRNA in HCC recurrence has not been investigated. Previous studies have indicated that the hsa-miR-24-3p miRNA is associated with many diseases, including atherosclerosis, 36 ischemic chest pain, 37 diabetes, 38 and Parkinson disease. 39 miR-24-3p plays a role in the development of multiple cancers.…”