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

Res Pract Thromb Haemost. 2024 Aug 23;8(6):102555. doi: 10.1016/j.rpth.2024.102555. eCollection 2024 Aug.

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.

Keywords: cardiovascular risk; fibrinogen; lipid peroxidation; liver transplant; oxidative stress.