Luqun Yang, Xin Guan, Jiangwei Cheng, Lin Ni, Huijing Yao, Yuping Gao, Kaiyi Zhu, Xiushan Shi, Bingjie Li, Yuanyuan Lin
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Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG), and Gene Set Enrichment Analysis (GSEA) were also conducted. Moreover, human umbilical vein endothelial cells (HUVECs) were cultured in circumstances characterized by elevated glucose levels to establish a cellular injury model simulating atherosclerotic conditions, and quantitative Polymerase Chain Reaction (qPCR) experiments were conducted to validate the differences of co-DEGs. Subsequently, the Summary-data-based Mendelian Randomization (SMR) method was employed. Additionally, we employed the Western Blot (WB) technique to validate the differential expression of VAMP8. Finally, we identified the differential expression of VAMP8 in the validation set and further validated its differential expression by collecting fresh blood samples from 20 patients with atherosclerosis and 20 healthy individuals.</p><p><strong>Results: </strong>14 co-DEGs (FABP5, GULP1, COL4A5, VAMP8, FABP4, PFN2, ANGPT2, TFPI2, NUPR1, SULF1, FGF13, BASP1, EPB41L3, and PBK) were identified. SMR analysis confirmed 10 potential causal effect genes: PSRC1, VAMP8, FES, HNRNPUL1, CFDP1, SAP130, MDN1, OPRL1, UTP11, and HOXC4. The qPCR and WB experiments demonstrated that VAMP8 was significantly upregulated in the injured HUVECs group (p < 0.0001). Compared to the control group, VAMP8 was markedly increased in the blood samples of patients with atherosclerosis (p < 0.0001).</p><p><strong>Conclusions: </strong>VAMP8 may potentially serve as a pathogenic gene in the process of endothelial dysfunction in atherosclerosis.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149231"},"PeriodicalIF":2.6000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"VAMP8 as a biomarker and potential therapeutic target for endothelial cell dysfunction in atherosclerosis.\",\"authors\":\"Luqun Yang, Xin Guan, Jiangwei Cheng, Lin Ni, Huijing Yao, Yuping Gao, Kaiyi Zhu, Xiushan Shi, Bingjie Li, Yuanyuan Lin\",\"doi\":\"10.1016/j.gene.2025.149231\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Endothelial cell dysfunction has a critical role in the pathophysiology of atherosclerosis. 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引用次数: 0
摘要
背景：内皮细胞功能障碍在动脉粥样硬化的病理生理中起着关键作用。本研究旨在揭示动脉粥样硬化中与内皮细胞功能障碍相关的关键基因和途径，并确定其可能的因果关系和潜在机制。方法：收集动脉粥样硬化中内皮细胞功能障碍相关数据集，分为训练集和验证集。在差异分析之后，我们构建了一个蛋白质-蛋白质相互作用（PPI）网络和一个已知参与动脉粥样硬化内皮细胞功能障碍的共同差异表达基因（co-DEGs）的分子相互作用图。进行了基因本体（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）。此外，将人脐血管内皮细胞（HUVECs）培养在葡萄糖水平升高的环境下，建立模拟动脉粥样硬化条件的细胞损伤模型，并进行定量聚合酶链反应（qPCR）实验验证共degs的差异。随后，采用基于汇总数据的孟德尔随机化（SMR）方法。此外，我们采用Western Blot （WB）技术验证VAMP8的差异表达。最后，我们确定了验证集中VAMP8的差异表达，并通过采集20例动脉粥样硬化患者和20例健康个体的新鲜血液样本进一步验证其差异表达。结果：共鉴定出14个共基因（FABP5、GULP1、COL4A5、VAMP8、FABP4、PFN2、ANGPT2、TFPI2、NUPR1、SULF1、FGF13、BASP1、EPB41L3、PBK）。SMR分析确认了10个潜在的致病基因：PSRC1、VAMP8、FES、HNRNPUL1、CFDP1、SAP130、MDN1、OPRL1、UTP11和HOXC4。qPCR和WB实验表明，VAMP8在HUVECs损伤组中表达显著上调（p ）。结论：VAMP8可能在动脉粥样硬化内皮功能障碍过程中发挥潜在的致病基因作用。
VAMP8 as a biomarker and potential therapeutic target for endothelial cell dysfunction in atherosclerosis.
Background: Endothelial cell dysfunction has a critical role in the pathophysiology of atherosclerosis. This study aims to uncover pivotal genes and pathways linked to endothelial cell dysfunction in atherosclerosis, as well as to ascertain the assumed causal effects and potential mechanisms.
Methods: Datasets relevant to endothelial cell dysfunction in atherosclerosis were collected and divided into training and validation sets. Following differential analysis, we constructed a protein-protein interaction (PPI) network and a molecular interaction map of common-differentially expressed genes (co-DEGs) with proteins known to be involved in atherosclerotic endothelial cell dysfunction. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG), and Gene Set Enrichment Analysis (GSEA) were also conducted. Moreover, human umbilical vein endothelial cells (HUVECs) were cultured in circumstances characterized by elevated glucose levels to establish a cellular injury model simulating atherosclerotic conditions, and quantitative Polymerase Chain Reaction (qPCR) experiments were conducted to validate the differences of co-DEGs. Subsequently, the Summary-data-based Mendelian Randomization (SMR) method was employed. Additionally, we employed the Western Blot (WB) technique to validate the differential expression of VAMP8. Finally, we identified the differential expression of VAMP8 in the validation set and further validated its differential expression by collecting fresh blood samples from 20 patients with atherosclerosis and 20 healthy individuals.
Results: 14 co-DEGs (FABP5, GULP1, COL4A5, VAMP8, FABP4, PFN2, ANGPT2, TFPI2, NUPR1, SULF1, FGF13, BASP1, EPB41L3, and PBK) were identified. SMR analysis confirmed 10 potential causal effect genes: PSRC1, VAMP8, FES, HNRNPUL1, CFDP1, SAP130, MDN1, OPRL1, UTP11, and HOXC4. The qPCR and WB experiments demonstrated that VAMP8 was significantly upregulated in the injured HUVECs group (p < 0.0001). Compared to the control group, VAMP8 was markedly increased in the blood samples of patients with atherosclerosis (p < 0.0001).
Conclusions: VAMP8 may potentially serve as a pathogenic gene in the process of endothelial dysfunction in atherosclerosis.
期刊介绍：
Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.
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