2-Methoxybenzoic acid ameliorates arterial thrombosis via inhibiting carbon anhydrase activity in platelet.

IF 5.5 2区医学 Q1 HEMATOLOGY

Journal of Thrombosis and Haemostasis Pub Date : 2025-03-06 DOI:10.1016/j.jtha.2025.02.027

Yunchong Liu, Zhengde Zhao, Xiuyi Huang, Ying Xiao, Na Li, Wenchao Yang, Ruijia Feng, Weiqi Feng, Ting Long, Haoliang Wu, Guiyan Peng, Sifan Chen, Guangqi Chang, Kan Huang, Zilun Li

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引用次数: 0

Abstract

Background: 2-Methoxybenzoic acid (2MOA) is a natural compound with potential salicylate-like effects; however, its impact on arterial thrombosis remains unclear. This study aims to investigate the effects of 2MOA on thrombogenesis and its underlying mechanisms.

Methods: FeCl₃-induced carotid artery injury and laser-induced cremaster artery injury thrombosis assays were utilized to explore the effect of 2MOA on thrombogenesis in vivo. Various ex vivo platelet function assays were conducted to evaluate the impacts of 2MOA on platelet activity. In addition, untargeted metabolomics analysis was performed to identify the alterations in intraplatelet metabolites following 2MOA treatment.

Results: We found that 2MOA significantly ameliorated thrombosis in a dose-dependent manner, without affecting the normal hemostasis in C57BL/6J mice. 2MOA suppressed platelet reactivity as indicated by decreased spreading, retraction, and aggregation in both mouse and human platelets. Metabolomics analysis revealed significantly alterations in purine metabolism following 2MOA treatment, which increased cyclic guanosine monophosphate (cGMP) production in platelets. Mechanistically, 2MOA inhibited the activity of carbonic anhydrase, leading to elevated intra-platelet cGMP level, and subsequent suppression of cytosolic phospholipase A2 phosphorylation.

Conclusion: Our study illustrates that 2MOA efficaciously inhibits platelet reactivity and alleviates thrombogenesis via suppressing carbonic anhydrase activity, which should be a promising reagent in the prevention and treatment of arterial thrombotic events.

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来源期刊

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.