Abstract
Background Neuropeptide levels are closely associated with the development and maintenance of atrial fibrillation (AF) after myocardial infarction (MI). This study was aimed at investigating the regulatory network that affects neuropeptide expression through transcription factor modulation. Methods We downloaded three datasets from the GEO database, and after performing differential and crosstabulation analyses, we screened out differentially expressed (DE) miRNAs and DEmRNAs coexpressed in AF and MI and performed DEmiRNA–DEmRNA pairing prediction; from which, we constructed a regulatory network. Subsequently, the hsa-miR-662-CREB1-VIP axis was obtained, and the role of CREB1 and VIP in the development of AF after MI was further revealed by single-cell analysis and prediction model construction. Results In this study, eight DEmRNAs and four miRNAs were screened. hsa-miR-662 was identified by database integration analysis to regulate the transcription factor CREB1, a potential transcriptional regulator in VIP. CREB1 and VIP are mainly enriched in pathways of energy metabolism, ion channels, and myocardial contraction. CREB1 and VIP were identified as biomarkers of the onset and prognosis of MI and AF. Conclusions In this study, the miR-662/CREB1/VIP regulatory pathway was constructed through integrated analysis of datasets, thus providing new ideas to study the mechanisms of AF development.
Highlights
Ischaemic heart disease (IHD) is a major threat to human health, and the rate of disability and mortality owing to IHD has been exponentially increasing worldwide since 1990, with approximately 82% of deaths and 89% of disability occurring because of IHD in developing countries [1]
Of the DEmRNAs found in atrial fibrillation (AF), five transcription factors (TFs) (ETV4, XBP1, SP1, CREB1, and NFKB1) and four regulated neuropeptides (VIP, NPPB, AGTR1, and AGT) or their receptors were identified and constituted seven TF-mRNA pairs
Gene Set Enrichment Analysis (GSEA) results demonstrated that the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with CREB1 were those involved in oxidative phosphorylation, neuroactive ligand–receptor interaction, and vascular smooth muscle contraction (Figure 5(a)), and the gene ontology (GO) pathways associated with CREB1 and vasoactive intestinal polypeptide (VIP) were those involved in inhibitory extracellular ligand-gated ion channel activity, ligand-gated anion channel activity, and ATP synthesis coupled electron transport (Supplementary Figure 4A)
Summary
Ischaemic heart disease (IHD) is a major threat to human health, and the rate of disability and mortality owing to IHD has been exponentially increasing worldwide since 1990, with approximately 82% of deaths and 89% of disability occurring because of IHD in developing countries [1]. Atrial fibrosis is an important pathophysiological factor in the development of AF and is closely associated with recurrence and complications of AF. Neuropeptide levels are closely associated with the development and maintenance of atrial fibrillation (AF) after myocardial infarction (MI). We downloaded three datasets from the GEO database, and after performing differential and crosstabulation analyses, we screened out differentially expressed (DE) miRNAs and DEmRNAs coexpressed in AF and MI and performed DEmiRNA–DEmRNA pairing prediction; from which, we constructed a regulatory network. Hsa-miR-662 was identified by database integration analysis to regulate the transcription factor CREB1, a potential transcriptional regulator in VIP. The miR-662/CREB1/VIP regulatory pathway was constructed through integrated analysis of datasets, providing new ideas to study the mechanisms of AF development
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