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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引用次数: 0
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.
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.