Insoluble proteomics analysis of acute intracranial large vessel occlusive thrombus.

IF 5.5 2区 医学 Q1 HEMATOLOGY Journal of Thrombosis and Haemostasis Pub Date : 2024-10-23 DOI:10.1016/j.jtha.2024.09.033
Liuchang He, Yunchao Wang, Hanghang Zhu, Kaihao Han, Sen Wei, Tao Quan, Panxing Li, Bo Yang, Ke Sun, Yazhou Jin, Anran Wang, Xinli Xue, Lei Zhang, Conghui Liu, Yuan Gao, Yuming Xu
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Abstract

Background: Acute large vessel occlusion (LVO) stroke is highly prevalent and severe. Despite thrombolytic therapy, many patients experience substantial complications. Understanding the origins, constituents, and pathologic processes involved in thrombus formation in acute intracranial large artery occlusion is crucial.

Objectives: To identify the characteristics of insoluble proteins from different sources of cerebral thrombus.

Methods: This study included 13 patients with cardiogenic embolic (CE) thrombus and 15 with large artery atherosclerotic (LAA) thrombus. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used to analyze insoluble proteins in thrombi. Bioinformatics analyses explored differential proteins and associated functional pathways. Least absolute shrinkage and selection operator and random forest identified biomarkers for diagnosing thrombus sources, validated by parallel reaction monitoring.

Results: We constructed an insoluble protein atlas of cerebral thrombi, identifying 6975 insoluble proteins, including 143 extracellular matrix (ECM)-related proteins. The enrichment pathways considerably varied between thrombi from different sources. Inflammation-related pathways, such as acute inflammatory response, along with ECM-related pathways such as laminin interactions, were notably upregulated in LAA compared with CE. Additionally, 2 biomarkers (IDH2 and HSPG2) exhibited strong diagnostic performance (area under the curve = 1) and robustness.

Conclusion: In the insoluble proteomics of thrombus, we highlighted the crucial roles of immune responses and ECM proteins in thrombus formation, providing new insights into its mechanisms and potential drug development. Additionally, we identified 2 biomarkers that offer new methods for determining thrombus sources in patients with LVO.

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急性颅内大血管闭塞性血栓的不溶性蛋白质组学分析
背景:急性大血管闭塞(LVO)脑卒中发病率高且病情严重。尽管进行了溶栓治疗,许多患者仍会出现严重并发症。了解急性颅内大动脉闭塞血栓形成的起源、成分和病理过程至关重要:目的:确定不同来源的脑血栓不溶性蛋白的特征:本研究包括13例心源性栓塞血栓(CE)患者和15例大动脉粥样硬化血栓(LAA)患者。采用高效液相色谱法和液相色谱-串联质谱法分析血栓中的不溶性蛋白质。生物信息学分析探索了差异蛋白质和相关功能途径。最小绝对收缩和选择运算器以及随机森林确定了诊断血栓来源的生物标志物,并通过平行反应监测进行了验证:我们构建了脑血栓不溶性蛋白图谱,识别了6975个不溶性蛋白,包括143个细胞外基质(ECM)相关蛋白。不同来源的脑血栓富集途径差异很大。与 CE 相比,炎症相关通路(如 "急性炎症反应")和 ECM 相关通路(如 "层粘连蛋白相互作用")在 LAA 中明显上调。此外,两个生物标记物(IDH2、HSPG2)表现出很强的诊断性能(AUC = 1)和稳健性:在血栓的不溶性蛋白质组学研究中,我们强调了免疫反应和 ECM 蛋白在血栓形成中的关键作用,为血栓形成机制和潜在药物开发提供了新的见解。此外,我们还发现了两种生物标志物,它们为确定左心室积液患者的血栓来源提供了新方法。
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来源期刊
Journal of Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis 医学-外周血管病
CiteScore
24.30
自引率
3.80%
发文量
321
审稿时长
1 months
期刊介绍: The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.
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