Oxidative stress–induced fibrinogen modifications in liver transplant recipients: unraveling a novel potential mechanism for cardiovascular risk

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2024-08-01 DOI:10.1016/j.rpth.2024.102555

{"title":"Oxidative stress–induced fibrinogen modifications in liver transplant recipients: unraveling a novel potential mechanism for cardiovascular risk","authors":"","doi":"10.1016/j.rpth.2024.102555","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Cardiovascular events represent a major cause of non–graft-related death after liver transplant. Evidence suggest that chronic inflammation associated with a remarkable oxidative stress in the presence of endothelial dysfunction and procoagulant environment plays a major role in the promotion of thrombosis. However, the underlying molecular mechanisms are not completely understood.</p></div><div><h3>Objectives</h3><p>In order to elucidate the mechanisms of posttransplant thrombosis, the aim of the present study was to investigate the role of oxidation-induced structural and functional fibrinogen modifications in liver transplant recipients.</p></div><div><h3>Methods</h3><p>A case-control study was conducted on 40 clinically stable liver transplant recipients and 40 age-matched, sex-matched, and risk factor–matched controls. Leukocyte reactive oxygen species (ROS) production, lipid peroxidation, glutathione content, plasma antioxidant capacity, fibrinogen oxidation, and fibrinogen structural and functional features were compared between patients and controls.</p></div><div><h3>Results</h3><p>Patients displayed enhanced leukocyte ROS production and an increased plasma lipid peroxidation with a reduced total antioxidant capacity compared with controls. This systemic oxidative stress was associated with fibrinogen oxidation with fibrinogen structural alterations. Thrombin-catalyzed fibrin polymerization and fibrin resistance to plasmin-induced lysis were significantly altered in patients compared with controls. Moreover, steatotic graft and smoking habit were associated with high fibrin degradation rate.</p></div><div><h3>Conclusion</h3><p>ROS-induced fibrinogen structural changes might increase the risk of thrombosis in liver transplant recipients.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002504/pdfft?md5=35fdaba75960d81f8bd6a4437c8506af&pid=1-s2.0-S2475037924002504-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Research and Practice in Thrombosis and Haemostasis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2475037924002504","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Cardiovascular events represent a major cause of non–graft-related death after liver transplant. Evidence suggest that chronic inflammation associated with a remarkable oxidative stress in the presence of endothelial dysfunction and procoagulant environment plays a major role in the promotion of thrombosis. However, the underlying molecular mechanisms are not completely understood.

Objectives

In order to elucidate the mechanisms of posttransplant thrombosis, the aim of the present study was to investigate the role of oxidation-induced structural and functional fibrinogen modifications in liver transplant recipients.

Methods

A case-control study was conducted on 40 clinically stable liver transplant recipients and 40 age-matched, sex-matched, and risk factor–matched controls. Leukocyte reactive oxygen species (ROS) production, lipid peroxidation, glutathione content, plasma antioxidant capacity, fibrinogen oxidation, and fibrinogen structural and functional features were compared between patients and controls.

Results

Patients displayed enhanced leukocyte ROS production and an increased plasma lipid peroxidation with a reduced total antioxidant capacity compared with controls. This systemic oxidative stress was associated with fibrinogen oxidation with fibrinogen structural alterations. Thrombin-catalyzed fibrin polymerization and fibrin resistance to plasmin-induced lysis were significantly altered in patients compared with controls. Moreover, steatotic graft and smoking habit were associated with high fibrin degradation rate.

Conclusion

ROS-induced fibrinogen structural changes might increase the risk of thrombosis in liver transplant recipients.

查看原文本刊更多论文

肝移植受者体内氧化应激诱导的纤维蛋白原改变：揭示心血管风险的新潜在机制

背景心血管事件是肝移植后非移植物相关死亡的主要原因。有证据表明，在内皮功能障碍和促凝环境下，与显著氧化应激相关的慢性炎症在促进血栓形成方面起着重要作用。为了阐明移植后血栓形成的机制，本研究旨在探讨氧化诱导的纤维蛋白原结构和功能改变在肝移植受者中的作用。方法对 40 例临床稳定的肝移植受者和 40 例年龄匹配、性别匹配和危险因素匹配的对照组进行了病例对照研究。结果与对照组相比，患者的白细胞活性氧（ROS）产生增加，血浆脂质过氧化增加，总抗氧化能力降低。这种全身性氧化应激与纤维蛋白原氧化和纤维蛋白原结构改变有关。与对照组相比，患者体内凝血酶催化的纤维蛋白聚合和纤维蛋白对凝血酶诱导的裂解的抵抗力发生了显著改变。结论ROS诱导的纤维蛋白原结构变化可能会增加肝移植受者血栓形成的风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊