GPVI deficiency reduces clot size and murine thrombosis in normoglycaemic but not hyperglycemic conditions.

IF 2.6 3区医学 Q3 CELL BIOLOGY

Platelets Pub Date : 2026-12-01 Epub Date: 2026-03-23 DOI:10.1080/09537104.2026.2646681

Julia S Gauer, Cédric Duval, Helen R McPherson, Amanda D V MacCannell, Lee D Roberts, Khalid M Naseem, Ramzi A Ajjan, Robert A S Ariëns

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引用次数: 0

Abstract

Background: Glycoprotein (GP)VI is involved in platelet activation, procoagulant phenotype development and reactive oxygen species (ROS) production. Patients with diabetes have altered platelet reactivity and abnormal clot structure, contributing to elevated thrombosis risk. The role of GPVI in clot formation in hyperglycemia is under-investigated.

Objectives: To compare the effect of GPVI-deficiency on ROS production and ex vivo and in vivo clot formation in normo- vs hyperglycemic mice.

Methods: Wild-type (WT) and GPVI-deficient (GPVI^-/-) mice had access to hyperglycemic (30% sucrose) or normoglycaemic (standard) diet for 8-weeks. ROS and mitochondrial activity (CS) were measured in isolated platelets. Clot contraction was performed with whole blood. Thrombus formation in vivo was assessed by inferior vena cava (IVC) ligation.

Results: Hyperglycemia increased ROS and CS activity in WT but not GPVI^-/- mice. Clot weight was decreased in GPVI^-/- vs WT mice in normoglycaemia, but these effects were lost in hyperglycemia. Clot weight after IVC ligation was reduced in GPVI^-/- vs WT mice in normoglycaemia, with the inverse observed in hyperglycemia.

Conclusions: Our data suggest that clot formation is affected differentially by absence of GPVI in normo- vs hyperglycemia, supporting a role for GPVI in thrombosis under normoglycaemic conditions only.

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GPVI缺乏降低了正常血糖状态下的凝块大小和小鼠血栓形成，而不是高血糖状态。

背景：糖蛋白（GP）VI参与血小板活化、促凝表型发育和活性氧（ROS）的产生。糖尿病患者血小板反应性改变，凝块结构异常，导致血栓形成风险升高。GPVI在高血糖患者血栓形成中的作用尚不清楚。目的：比较gpvi缺乏对正常和高血糖小鼠体内、体外ROS生成和凝块形成的影响。方法：野生型（WT）和GPVI缺乏（GPVI-/-）小鼠给予高血糖（30%蔗糖）或正常血糖（标准）饮食8周。测定离体血小板ROS和线粒体活性（CS）。用全血进行凝块收缩。通过下腔静脉结扎术评估体内血栓形成情况。结果：高血糖增加了WT小鼠的ROS和CS活性，而GPVI-/-小鼠没有。在正常血糖状态下，GPVI-/-与WT相比，凝块重量降低，但在高血糖状态下，这些作用消失。在正常血糖状态下，GPVI-/-与WT小鼠相比，结扎IVC后的凝块重量减少，在高血糖状态下观察到相反的情况。结论：我们的数据表明，在正常血糖和高血糖状态下，GPVI缺乏对血栓形成的影响是不同的，这支持了GPVI仅在正常血糖条件下对血栓形成的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Platelets 医学-细胞生物学

CiteScore

6.70

自引率

3.00%

发文量

审稿时长

1 months

期刊介绍： Platelets is an international, peer-reviewed journal covering all aspects of platelet- and megakaryocyte-related research. Platelets provides the opportunity for contributors and readers across scientific disciplines to engage with new information about blood platelets. The journal’s Methods section aims to improve standardization between laboratories and to help researchers replicate difficult methods. Research areas include: Platelet function Biochemistry Signal transduction Pharmacology and therapeutics Interaction with other cells in the blood vessel wall The contribution of platelets and platelet-derived products to health and disease The journal publishes original articles, fast-track articles, review articles, systematic reviews, methods papers, short communications, case reports, opinion articles, commentaries, gene of the issue, and letters to the editor. Platelets operates a single-blind peer review policy. Authors can choose to publish gold open access in this journal.