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.
Oxidative stress–induced fibrinogen modifications in liver transplant recipients: unraveling a novel potential mechanism for cardiovascular risk / Gitto, Stefano; Fiorillo, Claudia; Argento, Flavia Rita; Fini, Eleonora; Borghi, Serena; Falcini, Margherita; Roccarina, Davide; La Delfa, Rosario; Lillo, Ludovica; Zurli, Tommaso; Forte, Paolo; Ghinolfi, Davide; De Simone, Paolo; Chiesi, Francesca; Ingravallo, Angelica; Vizzutti, Francesco; Aspite, Silvia; Laffi, Giacomo; Lynch, Erica; Petruccelli, Stefania; Carrai, Paola; Palladino, Simona; Sofi, Francesco; Stefani, Laura; Amedei, Amedeo; Baldi, Simone; Toscano, Arianna; Lau, Chloe; Marra, Fabio; Becatti, Matteo. - In: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS. - ISSN 2475-0379. - ELETTRONICO. - 8:(2024), pp. 0-0. [10.1016/j.rpth.2024.102555]
Oxidative stress–induced fibrinogen modifications in liver transplant recipients: unraveling a novel potential mechanism for cardiovascular risk
Gitto, Stefano
;Fiorillo, Claudia;Argento, Flavia Rita;Fini, Eleonora;Borghi, Serena;Falcini, Margherita;Roccarina, Davide;La Delfa, Rosario;Zurli, Tommaso;De Simone, Paolo;Chiesi, Francesca;Ingravallo, Angelica;Vizzutti, Francesco;Aspite, Silvia;Laffi, Giacomo;Lynch, Erica;Petruccelli, Stefania;Sofi, Francesco;Stefani, Laura;Amedei, Amedeo;Baldi, Simone;Marra, Fabio;Becatti, Matteo
2024
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.File | Dimensione | Formato | |
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