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image of Exploring Mechanisms of Ephx2 in Treating Atherosclerosis Using Independent Cascade Model and Adverse Outcome Pathways

Abstract

Background

Atherosclerosis (AS) is a leading cause of cardiovascular diseases, characterized by lipid accumulation in arterial walls. The gene Ephx2, which encodes soluble epoxide hydrolase (sEH), is implicated in AS development, but its precise mechanisms and therapeutic potential are not fully understood.

Objectives

This study aimed to analyze gene expression data from low-density lipoprotein receptor knockout (LDLR−/−) and LDLR−/−sEH−/− mice to identify significant genes associated with AS.

Methods

A directed compound-protein interaction network was constructed based on these genes and related pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In the end, through resistance distance (RD) between any two nodes in this network, the Independent Cascade (IC) model was applied to explore Ephx2 mechanisms in AS, such as important Adverse Outcome Pathways (AOPs).

Results

Several AOPs were identified as critical in AS treatment Ephx2. The key AOPs included inflammatory response and cytokine release, cholesterol deposition and oxidation, disruption of plaque stability, smooth muscle cell proliferation and migration, and platelet activation and coagulation. Within the top AOPs of inflammatory response and cytokine release, potential target genes were identified, such as Mapk3, Pik3cd, Gnai2, Mapk10, Arnt, and RhoA. Critical paths from Ephx2 to these target genes were established, suggesting mechanisms by which Ephx2 may influence AS pathogenesis.

Conclusion

By defining the AS network and corresponding RD, this study elucidates potential mechanisms by which Ephx2 affects AS through specific KEGG pathways, AOPs, and target genes. These findings enhanced the understanding of AS pathogenesis and highlighte potential targets like Mapk3 for developing therapeutic strategies in AS prevention and treatment.

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2025-03-27
2025-09-14

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Exploring Mechanisms of Ephx2 in Treating Atherosclerosis Using Independent Cascade Model and Adverse Outcome Pathways
Bentham Science Publishers ; https://doi.org/10.2174/0113862073345542250220051427
/content/journals/cchts/10.2174/0113862073345542250220051427
/content/journals/cchts/10.2174/0113862073345542250220051427
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Supplements

Supplementary material is available on the publisher’s website along with the published article. Supplementary material 1: Significance analysis results: Result_Sig.rda Supplementary material 2: Genes related to Ephx2, their resistance distance, and depth Supplementary material 3: Genes in five AOPs Supplementary material 4: Adjacency matrix named as Adjacency_Ephx.rda

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  • Article Type:     Research Article
Keywords: resistance distance ; soluble epoxide hydrolase ; Atherosclerosis ; Ephx2 ; adverse outcome pathway ; independent cascade model

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