Jakub Siudut1, Joanna Natorska1, Michal Zabczyk2, Dorota Zajac3, Karolina Seweryn4, Maria Rąpała-Kozik4, Anetta Undas5. 1. Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland; Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. 2. Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. 3. Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. 4. Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. 5. Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland; Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. Electronic address: mmundas@cyf-kr.edu.pl.
Abstract
INTRODUCTION: Venous thromboembolism (VTE) is associated with hypofibrinolysis. Its mechanisms are poorly understood. We investigated plasminogen-fibrin interaction and its association with fibrinolytic capacity and protein oxidation/carbonylation in VTE patients. MATERIALS AND METHODS: Plasma-purified plasminogen conversion to plasmin and surface plasmon resonance employed for plasminogen-fibrin interactions were individually evaluated in all healthy controls and non-anticoagulated patients following VTE, 10-23months since the event. We also assessed plasma fibrin clot permeability (Ks), clot lysis time (LT), activators and inhibitors of fibrinolysis together with oxidation/carbonylation markers. RESULTS: VTE patients had impaired plasminogen binding to fibrin (apparent Kd, +290%, p=0.002), reduced rate of plasmin generation (-4.7%, p=0.001), and longer LT (+18.6%, p<0.001) compared with controls. Fibrinogen and Ks were similar in both groups. Apparent Kd correlated with LT (r=0.43, p=0.037), tissue plasminogen activator-plasminogen activator inhibitor 1 (tPA-PAI-1) complexes (r=0.63, p=0.012), and active PAI-1 (r=0.49, p=0.03). Compared with controls, VTE patients had higher thiobarbituric acid reactive substances (TBARS), total protein carbonyl content (PC), and lower total antioxidant capacity (all p<0.001), that all were associated with LT (r=0.61, r=0.56, and r=-0.47, respectively, all p<0.05). Impaired plasminogen binding to fibrin reflected by apparent Kd positively correlated with TBARS (r=0.48, p=0.032) and PC (r=0.54, p=0.013) in the whole group. CONCLUSIONS: Plasminogen-fibrin interactions are altered in young and middle-aged VTE patients, without known thrombophilias, except increased factor VIII. The mechanisms underlying these phenomena remain to be established.
INTRODUCTION:Venous thromboembolism (VTE) is associated with hypofibrinolysis. Its mechanisms are poorly understood. We investigated plasminogen-fibrin interaction and its association with fibrinolytic capacity and protein oxidation/carbonylation in VTEpatients. MATERIALS AND METHODS: Plasma-purified plasminogen conversion to plasmin and surface plasmon resonance employed for plasminogen-fibrin interactions were individually evaluated in all healthy controls and non-anticoagulated patients following VTE, 10-23months since the event. We also assessed plasma fibrin clot permeability (Ks), clot lysis time (LT), activators and inhibitors of fibrinolysis together with oxidation/carbonylation markers. RESULTS:VTEpatients had impaired plasminogen binding to fibrin (apparent Kd, +290%, p=0.002), reduced rate of plasmin generation (-4.7%, p=0.001), and longer LT (+18.6%, p<0.001) compared with controls. Fibrinogen and Ks were similar in both groups. Apparent Kd correlated with LT (r=0.43, p=0.037), tissue plasminogen activator-plasminogen activator inhibitor 1 (tPA-PAI-1) complexes (r=0.63, p=0.012), and active PAI-1 (r=0.49, p=0.03). Compared with controls, VTEpatients had higher thiobarbituric acid reactive substances (TBARS), total protein carbonyl content (PC), and lower total antioxidant capacity (all p<0.001), that all were associated with LT (r=0.61, r=0.56, and r=-0.47, respectively, all p<0.05). Impaired plasminogen binding to fibrin reflected by apparent Kd positively correlated with TBARS (r=0.48, p=0.032) and PC (r=0.54, p=0.013) in the whole group. CONCLUSIONS: Plasminogen-fibrin interactions are altered in young and middle-aged VTEpatients, without known thrombophilias, except increased factor VIII. The mechanisms underlying these phenomena remain to be established.
Authors: Grzegorz Gajos; Aleksander Siniarski; Joanna Natorska; Michał Ząbczyk; Jakub Siudut; Krzysztof Piotr Malinowski; Renata Gołębiowska-Wiatrak; Paweł Rostoff; Anetta Undas Journal: Cardiovasc Diabetol Date: 2018-11-22 Impact factor: 9.951