Comprehensive analysis of the diagnostic and therapeutic value of the hypoxia- related gene PLAUR in the progression of atherosclerosis-Reference-Cited by-同舟云学术

Comprehensive analysis of the diagnostic and therapeutic value of the hypoxia- related gene PLAUR in the progression of atherosclerosis

Published:2023-02-23 Issue: Volume: Page:
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Author:

Dai Chengyi¹,Lin Yuhang²

Affiliation:

1. The First People's Hospital of Xiaoshan District

2. the First Affiliated Hospital of Wenzhou Medical University

Abstract

Abstract Atherosclerosis (AS) is a major contributor to a variety of negative clinical outcomes, including stroke and myocardial infarction. The progression of the lesion is accompanied by a decrease in oxygen diffusion in the area of the plaque. Our research aims to reveal whether hypoxia-related genes are involved in the occurrence and development of AS, and whether they have potential diagnostic and therapeutic value. Combined with the results of differential expression genes (DEG) analysis, weighted gene co-expression network analysis (WGCNA), and random forest analysis, the key hypoxia-related genes highly related to AS progression were selected. To investigate differences in immune infiltration in lesions and the relationship between hypoxia and immune infiltration, single-sample gene set enrichment analysis (ssGSEA), ESTIMATE, and CIBERSORT analyses were performed. On the basis of TarBase, MirTarBase, and DIANA databases, a competitive endogenous RNA (ceRNA) network was constructed to regulate the expression of key gene. Use the DrugMatrix database to predict targeted drugs, and use AutoDock to verify the binding ability of drugs and proteins. We found that hypoxia was prominent in advanced-stage plaques and that there was a broad correlation between the hypoxia microenvironment and immune infiltration. The PLAUR gene has been identified as an effective diagnostic marker for the progression of AS lesions. PLAUR was positively correlated with HIF1A expression and macrophage infiltration in plaques. We predicted that HCG17-hsa-miR-424-5p-HIF1A is a ceRNA network that regulates PLAUR expression. Finally, alprostadil, valsartan, biotin A, luteolin, and curcumin were predicted as potential drugs to delay lesion progression by antagonizing PLAUR. This research has significant implications for the search for new treatment targets and disease prevention as it advances our understanding of the molecular mechanisms that underpin the role of hypoxia in AS progression.

Publisher

Research Square Platform LLC

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