乙醛暴露改变体外纤维蛋白聚合、纤维蛋白溶解和纤维蛋白网络结构

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2025-05-01 DOI:10.1016/j.rpth.2025.102921

Shakthi Rave , Daniel P. Hu , Rebecca A. Risman , Warishah Khan , Valerie Tutwiler , Lauren G. Poole

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引用次数: 0

摘要

背景纤维蛋白（原）是血凝块的主要结构成分，在血栓形成和止血中起着关键作用。在炎症和疾病期间暴露于反应性内源性代谢物或外源物时，纤维蛋白原的翻译后修饰会改变聚合物的形成、网络结构或对裂解的易感性。乙醛是肝脏乙醇代谢的反应副产物，是一种普遍存在的环境污染物，与大分子形成稳定的加合物。先前的研究报道，乙醛损害多种凝血因子的功能，包括纤维蛋白原。目的本研究旨在验证纤维蛋白原暴露于乙醛会改变纤维蛋白聚合、凝块结构和纤维蛋白溶解的假设。方法纤维蛋白原与0、90、180、270 mM乙醛共孵育30分钟，透析去除过量乙醛。评估纤维蛋白聚合、凝块结构和纤维蛋白溶解。结果浊度曲线分析表明，与对照组相比，暴露于180和270 mM乙醛显著降低凝血酶驱动的纤维蛋白形成率和最大吸光度。浊度分析和完全形成的血块的扫描电子显微镜显示，乙醛暴露（180和270 mM）导致形成更密集的薄纤维纤维蛋白网络。最后，乙醛暴露倾向于通过纤溶酶加速完全形成的凝块的外部裂解。相比之下，当纤维蛋白原与组织纤溶酶原激活剂和纤溶酶原在凝块形成前孵育时，乙醛显著延迟了内部凝块的溶解。这些结果表明，乙醛暴露驱动血栓前纤维蛋白凝块的形成，这些凝块对溶解具有抗性，这表明内源性或外源性乙醛暴露可能影响血栓形成的风险。

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Acetaldehyde exposure alters fibrin polymerization, fibrinolysis, and fibrin network structure in vitro

Background

Fibrin(ogen), the primary structural component of blood clots, plays a critical role in thrombosis and hemostasis. Posttranslational modifications to fibrinogen that occur upon exposure to reactive endogenous metabolites or xenobiotics during inflammation and disease alter polymer formation, network structure, or susceptibility to lysis. Acetaldehyde is a reactive byproduct of hepatic ethanol metabolism and ubiquitous environmental pollutant that forms stable adducts with macromolecules. Previous studies report that acetaldehyde impairs the function of multiple coagulation factors, including fibrinogen.

Objectives

The study aimed to test the hypothesis that exposure of fibrinogen to acetaldehyde alters fibrin polymerization, clot structure, and fibrinolysis.

Methods

Fibrinogen was incubated with 0, 90, 180, or 270 mM acetaldehyde for 30 minutes and then dialyzed to remove excess acetaldehyde. Fibrin polymerization, clot structure, and fibrinolysis were assessed.

Results

Analysis of turbidity curves indicated that exposure to 180 and 270 mM acetaldehyde significantly decreased the rate of thrombin-driven fibrin formation and the maximum absorbance compared to control. Turbidimetric analysis and scanning electron microscopy of fully formed clots revealed that acetaldehyde exposure (180 and 270 mM) caused formation of more densely packed fibrin networks of thin fibers. Finally, acetaldehyde exposure tended to accelerate the external lysis of fully formed clots by plasmin. In contrast, acetaldehyde significantly delayed internal clot lysis when fibrinogen was incubated with tissue plasminogen activator and plasminogen before clot formation.

Conclusions

These results indicate that acetaldehyde exposure drives the formation of prothrombotic fibrin clots that are resistant to lysis, suggesting that endogenous or exogenous acetaldehyde exposure may influence thrombosis risk.

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