Molecular structure of VEGFA polysaccharide protein and its regulation of monocyte infiltration and oxidative stress after myocardial infarction

IF 8.5 1区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Biological Macromolecules Pub Date : 2025-04-19 DOI:10.1016/j.ijbiomac.2025.143199
Zhenyu Huang , Bohan Wen , Ming Wang , Yanqiao Lu , Qingqi Ji , Ju Mei , Xin Shi , Zhaolei Jiang
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Abstract

The pathogenesis of myocardial infarction (MI) is complex, involving multiple biomarkers and cell signaling pathways. The aim of this study was to elucidate the molecular structure of VEGFA dioglycan protein and explore how it regulates monocyte infiltration and oxidative stress response after myocardial infarction, so as to provide a new molecular target for the treatment of myocardial infarction. Differential expression analysis and enrichment analysis were performed to investigate the composition and characteristics of immune cells in myocardial infarction. The regulatory network was constructed by network analysis, and in vitro experiments were carried out by BMDM isolation culture. Animal experiments were conducted in mouse models, and data were verified and statistically analyzed by combining immunohistochemical staining, real-time PCR, Western blot and enzyme-linked immunosorbent assay (ELISA). Genome-wide association studies (GWAS) and single-cell data successfully identified key immune-related genes and analyzed differentially expressed mRNA and its characteristics in myocardial infarction. The immune microenvironment of myocardial infarction was investigated, the differentially expressed circRNA and miRNA were characterized, and the circrNa-mirNA-mrna regulatory network was constructed. The characteristics of differentially expressed proteins in myocardial infarction and the changes of mRNA during oxidative stress were identified and compared. By analyzing the changes in chromatin accessibility, the regulatory network between oxidative stress and myocardial infarction in immune cells was constructed, and the expression and co-localization of oxidative stress in myocardial infarction were verified.
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VEGFA多糖蛋白的分子结构及其对心肌梗死后单核细胞浸润和氧化应激的调节作用
心肌梗死(MI)的发病机制复杂,涉及多种生物标志物和细胞信号通路。本研究旨在阐明VEGFA二聚糖蛋白的分子结构,探讨其如何调控心肌梗死后单核细胞浸润和氧化应激反应,为心肌梗死的治疗提供新的分子靶点。通过差异表达分析和富集分析,探讨心肌梗死免疫细胞的组成和特征。通过网络分析构建调控网络,并通过BMDM分离培养进行体外实验。动物实验建立小鼠模型,结合免疫组织化学染色、实时荧光定量PCR、Western blot和酶联免疫吸附试验(ELISA)对数据进行验证和统计分析。全基因组关联研究(GWAS)和单细胞数据成功鉴定了关键的免疫相关基因,并分析了心肌梗死中mRNA的差异表达及其特征。研究心肌梗死的免疫微环境,对差异表达的circRNA和miRNA进行表征,构建circRNA - miRNA -mrna调控网络。鉴定并比较心肌梗死组织中差异表达蛋白的特征及氧化应激过程中mRNA的变化。通过分析染色质可及性的变化,构建免疫细胞氧化应激与心肌梗死的调控网络,验证氧化应激在心肌梗死中的表达和共定位。
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来源期刊
International Journal of Biological Macromolecules
International Journal of Biological Macromolecules 生物-生化与分子生物学
CiteScore
13.70
自引率
9.80%
发文量
2728
审稿时长
64 days
期刊介绍: The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.
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