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引用次数: 0
摘要
背景:急性心肌梗死(AMI)是一种严重的心血管事件,其特点是冠状动脉血流突然中断,导致心肌缺血和坏死。尽管急性治疗措施取得了进展,但对急性心肌梗死相关代谢损伤的了解,特别是通过特定蛋白质表达的了解仍然有限。本研究利用Olink心血管代谢组学技术探索与AMI相关的心血管代谢相关蛋白生物标志物,旨在满足早期诊断和靶向治疗的临床需求:本研究利用Olink心血管代谢组学技术分析了20名AMI患者和10名健康对照者冠状动脉血液样本中的92种心血管代谢相关蛋白。利用统计学 t 检验确定了差异表达的蛋白质,随后进行了功能富集分析(GO 和 KEGG)和蛋白质-蛋白质相互作用网络构建。通过酶联免疫吸附测定法,在另外 125 名 AMI 患者和 120 名健康对照者的血浆样本中验证了五种核心蛋白质。为了评估诊断性能,利用GEO相关数据集生成了接收者操作特征曲线,并采用孟德尔随机分析法研究了核心蛋白与AMI风险之间的因果关系:结果:研究发现32种蛋白质在AMI患者和健康对照组之间的表达水平有显著变化。其中,五种核心蛋白-PCOLCE、FCN2、REG1A、DEFA1和CRTAC1与新陈代谢、胶原形成和PI3K/AKT信号通路等关键生物过程密切相关。这些蛋白质与 BMI、LVEF、NT-proBNP、CK-MB 和 cTnT 等临床指标有很强的相关性。FCN2和DEFA1与急性心肌梗死风险的因果关系得到了进一步验证,表明它们具有作为诊断生物标志物的潜力:结论:已确定的核心蛋白 PCOLCE、FCN2、REG1A、DEFA1 和 CRTAC1 是早期诊断和评估急性心肌梗死风险的潜在生物标志物。这些研究结果表明,这些蛋白质可作为未来治疗干预的目标,以减轻急性心肌梗死对心血管的代谢损伤。
Identification of Cardiometabolic Protein Biomarkers for Acute Myocardial Infarction Using Olink Proteomics.
Background: Acute myocardial infarction (AMI) is a critical cardiovascular event characterized by sudden coronary blood flow interruption, leading to myocardial ischemia and necrosis. Despite advances in acute therapeutic measures, understanding the metabolic damage related to AMI, particularly through specific protein expressions, remains limited. This study utilized Olink cardiovascular metabolomics technology to explore cardiovascular metabolism-related protein biomarkers associated with AMI, aiming to address the clinical need for early diagnosis and targeted therapy.
Methods: This study utilized Olink cardiovascular metabolomics technology to analyze 92 cardiovascular metabolism-related proteins in coronary blood samples from 20 AMI patients and 10 healthy controls. Differentially expressed proteins were identified using statistical t-tests, followed by functional enrichment analysis (GO and KEGG) and protein-protein interaction network construction. Five core proteins were validated in plasma samples from an additional 125 AMI patients and 120 healthy controls via enzyme-linked immunosorbent assay. To evaluate diagnostic performance, receiver operating characteristic curves were generated using GEO-related datasets, and Mendelian randomization analysis was employed to investigate the causal relationship between core proteins and AMI risk.
Results: The study identified 32 proteins with significantly altered expression levels between AMI patients and healthy controls. Among these, five core proteins-PCOLCE, FCN2, REG1A, DEFA1, and CRTAC1-were significantly associated with key biological processes such as metabolism, collagen formation, and the PI3K/AKT signaling pathway. These proteins showed strong correlations with clinical indicators, including BMI, LVEF, NT-proBNP, CK-MB, and cTnT. FCN2 and DEFA1 were further validated as having a causal relationship with AMI risk, indicating their potential as diagnostic biomarkers.
Conclusion: The identified core proteins PCOLCE, FCN2, REG1A, DEFA1, and CRTAC1 are potential biomarkers for the early diagnosis and risk assessment of AMI. These findings suggest that these proteins could serve as targets for future therapeutic interventions aimed at mitigating cardiovascular metabolic damage in AMI.
期刊介绍:
An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.