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Published on: August 20, 2019
Effects of Atherogenic Factors on Endothelial Cells: Bioinformatics Analysis of Differentially Expressed Genes and
1Department of Nursing, Ryazan State Medical University, 390026 Ryazan, Russia.
Insights
Atherosclerosis develops from endothelial cell dysfunction caused by smoking, poor blood flow, and oxidized LDL. These factors impair immune response, metabolism, and apoptosis, driving disease progression.
Area of Science:
- Cardiovascular Biology
- Bioinformatics
- Molecular Medicine
Background:
- Atherosclerosis is a chronic vascular disease with significant morbidity and mortality.
- It involves complex cellular events within the vascular wall influenced by multiple factors.
- Understanding these molecular mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the gene ontology of differentially expressed genes (DEGs) in endothelial cells exposed to atherogenic factors.
- To identify key biological processes and signaling pathways implicated in atherosclerosis development.
- To utilize bioinformatic analysis of Gene Expression Omnibus (GEO) datasets.
Main Methods:
- Bioinformatic analysis of GEO datasets.
- Identification of DEGs using the limma R package.
- Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) network analysis.
Main Results:
- DEGs were primarily involved in cytokine-mediated signaling, innate immune response, lipid biosynthesis, and nitric-oxide synthase activity.
- Enriched KEGG pathways included tumor necrosis factor, NF-κB signaling, NOD-like receptor signaling, and pathways related to lipid metabolism and apoptosis.
- Atherogenic factors significantly impact endothelial cell function.
Conclusions:
- Atherosclerosis is driven by endothelial cell dysfunction induced by factors like smoking, impaired flow, and oxidized LDL.
- These factors disrupt innate immune responses, cellular metabolism, and apoptosis, contributing to atherosclerosis.
- Targeting these pathways may offer therapeutic strategies for atherosclerosis.
Abstract:
(1) Background: Atherosclerosis is a serious medical condition associated with high morbidity and mortality rates. It develops over many years as a complex chain of events in the vascular wall involving various cells and is influenced by many factors of clinical interest. (2) Methods: In this study, we performed a bioinformatic analysis of Gene Expression Omnibus (GEO) datasets to investigate the gene ontology of differentially expressed genes (DEGs) in endothelial cells exposed to atherogenic factors such as tobacco smoking, oscillatory shear, and oxidized low-density lipoproteins (oxLDL). DEGs were identified using the limma R package, and gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) network analysis were performed. (3) Results: We studied biological processes and signaling pathways involving DEGs in endothelial cells under the influence of atherogenic factors. GO enrichment analysis demonstrated that the DEGs were mainly involved in cytokine-mediated signaling pathway, innate immune response, lipid biosynthetic process, 5-lipoxygenase activity, and nitric-oxide synthase activity. KEGG pathway enrichment analysis showed that common pathways included tumor necrosis factor signaling pathway, NF-κB signaling pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis, lipoprotein particle binding, and apoptosis. (4) Conclusions: Atherogenic factors such as smoking, impaired flow, and oxLDL contribute to impaired innate immune response, metabolism, and apoptosis in endothelial cells, potentially leading to the development of atherosclerosis.
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