Chen Siqi, Hu Ziliang, Zhao Mingyue, Sun Jie, Nie Sheng, Gao Xiang, Huang Yi
Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang 315010, China.
Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China.
J Proteomics. 2025 Mar 20;313:105374. doi: 10.1016/j.jprot.2025.105374. Epub 2025 Jan 4.
Inflammation is a complex factor in the pathogenesis of intracranial aneurysms (IA), but its specific cellular inflammatory factors remain uncertain. We collected two cohorts and measured the representation of vascular inflammation-related proteins using the Olink CVD II Vascular Inflammation Panel. We subsequently validated our findings using ELISA and RT-qPCR. Our proteomic analysis identified 11 vascular inflammation-related markers that were significantly differentially represented between the IA and control groups. These markers were implicated in leukocyte migration, immune response, triglyceride and lipoprotein metabolism, acute phase response, T cell regulation, and several key biological pathways, including PPAR, HIF-1, cytokine-cytokine interactions, and PI3K-AKT signaling. Further validation with ELISA and RT-qPCR confirmed the differential representation of IL6, PTX3, LPL, and OLR1 between the two groups. Notably, a combination marker incorporating these four factors demonstrated high diagnostic potential for the early detection of IA. Our study has identified a set of informative biomarkers (IL6, PTX3, LPL, and OLR1) that could be valuable for the early diagnosis of IA. Importantly, this is the first report of significantly elevated OLR1 representation in the plasma of IA patients. Further investigation into the role of OLR1 in the pathogenesis of IA is warranted. SIGNIFICANCE: This study significantly advances our understanding of the molecular mechanisms underlying intracranial aneurysm (IA) pathogenesis. By identifying a panel of novel biomarkers, including the previously unreported elevated expression of OLR1 in IA patients, we provide crucial insights into the inflammatory processes involved in aneurysm formation and development. These findings have important clinical implications, as the identified biomarkers could serve as valuable tools for early diagnosis and potentially targeted therapeutic interventions. Furthermore, the study highlights the complex interplay of inflammatory pathways in IA, suggesting that a multi-faceted approach may be necessary for effective management.
炎症是颅内动脉瘤（IA）发病机制中的一个复杂因素，但其具体的细胞炎症因子仍不明确。我们收集了两个队列，并使用Olink CVD II血管炎症检测板测量了血管炎症相关蛋白的表达情况。随后，我们使用酶联免疫吸附测定（ELISA）和逆转录定量聚合酶链反应（RT-qPCR）对我们的研究结果进行了验证。我们的蛋白质组学分析确定了11种血管炎症相关标志物，这些标志物在IA组和对照组之间存在显著差异表达。这些标志物与白细胞迁移、免疫反应、甘油三酯和脂蛋白代谢、急性期反应、T细胞调节以及几个关键的生物学途径有关，包括过氧化物酶体增殖物激活受体（PPAR）、缺氧诱导因子-1（HIF-1）、细胞因子-细胞因子相互作用以及磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-AKT）信号通路。ELISA和RT-qPCR的进一步验证证实了两组之间白细胞介素6（IL6）、五聚素3（PTX3）、脂蛋白脂肪酶（LPL）和氧化低密度脂蛋白受体1（OLR1）的差异表达。值得注意的是，包含这四个因素的组合标志物对IA的早期检测具有很高的诊断潜力。我们的研究确定了一组信息丰富的生物标志物（IL6、PTX3、LPL和OLR1），这些标志物对IA的早期诊断可能具有重要价值。重要的是，这是首次报道IA患者血浆中OLR1表达显著升高。有必要进一步研究OLR1在IA发病机制中的作用。意义：本研究显著推进了我们对颅内动脉瘤（IA）发病机制潜在分子机制的理解。通过鉴定一组新的生物标志物，包括IA患者中先前未报道的OLR1表达升高，我们为动脉瘤形成和发展过程中的炎症过程提供了关键见解。这些发现具有重要的临床意义，因为所鉴定的生物标志物可作为早期诊断和潜在靶向治疗干预的有价值工具。此外，该研究突出了IA中炎症途径的复杂相互作用，表明可能需要采取多方面的方法进行有效管理。
