Rave Shakthi, Hu Daniel P, Risman Rebecca A, Khan Warishah, Tutwiler Valerie, Poole Lauren G
Department of Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, USA.
Department of Biomedical Engineering, Rutgers School of Engineering, Piscataway, New Jersey, USA.
Res Pract Thromb Haemost. 2025 Jun 6;9(4):102921. doi: 10.1016/j.rpth.2025.102921. eCollection 2025 May.
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.
The study aimed to test the hypothesis that exposure of fibrinogen to acetaldehyde alters fibrin polymerization, clot structure, and fibrinolysis.
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.
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.
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.
纤维蛋白（原）是血凝块的主要结构成分，在血栓形成和止血过程中起关键作用。在炎症和疾病期间，当纤维蛋白原暴露于反应性内源性代谢产物或外源性物质时，发生的翻译后修饰会改变聚合物形成、网络结构或对溶解的敏感性。乙醛是肝脏乙醇代谢的反应性副产物和普遍存在的环境污染物，可与大分子形成稳定的加合物。先前的研究报告称，乙醛会损害包括纤维蛋白原在内的多种凝血因子的功能。
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这一假设。
将纤维蛋白原与0、90、180或270 mM乙醛孵育30分钟，然后透析以去除过量的乙醛。评估纤维蛋白聚合、凝块结构和纤维蛋白溶解情况。
浊度曲线分析表明，与对照组相比，暴露于180和270 mM乙醛会显著降低凝血酶驱动的纤维蛋白形成速率和最大吸光度。对完全形成的凝块进行比浊分析和扫描电子显微镜观察发现，暴露于乙醛（180和270 mM）会导致形成更密集堆积的细纤维纤维蛋白网络。最后，乙醛暴露倾向于加速纤溶酶对完全形成的凝块的外部溶解。相比之下，当在凝块形成前将纤维蛋白原与组织纤溶酶原激活剂和纤溶酶原一起孵育时，乙醛会显著延迟凝块的内部溶解。
这些结果表明，乙醛暴露会促使形成抗溶解的促血栓纤维蛋白凝块，提示内源性或外源性乙醛暴露可能会影响血栓形成风险。
