Kazunari Maekawa1, Chihiro Sugita2, Atsushi Yamashita3, Sayaka Moriguchi-Goto4, Eiji Furukoji5, Tatefumi Sakae5, Toshihiro Gi1, Toshinori Hirai5, Yujiro Asada1. 1. Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. 2. Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan; Department of Biochemistry, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka 882-0072, Japan. 3. Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. Electronic address: atsushi_yamashita@med.miyazaki-u.ac.jp. 4. Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan; Department of Pathology, Miyazaki Prefectural Hospital, 5-30 Kitatakamatsu, Miyazaki 880-5810, Japan. 5. Department of Radiology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Abstract
BACKGROUND: Thrombolytic therapy is effective in fresh deep vein thrombosis (DVT) although the benefit may fall below the risk of bleeding in non-fresh thrombosis. Markers reflecting fresh DVT have not been established. The present study aims to identify metabolites reflecting fresh venous thrombus and their role in thrombus formation. METHODS: Metabolites of rabbit venous blood and jugular venous thrombus 4 h after thrombus induction were analysed using electrophoresis-time of flight mass spectrometry. The effects of the altered metabolites on blood coagulation and platelet aggregation were assessed by using rotation thromboelastometry and platelet aggregometer. Cellular contents and glucose transporter (Glut)-1 expression in aspirated human DVT samples were pathologically analysed. RESULTS: Metabolome analysis identified 226 metabolites (133 cationic and 93 anionic metabolites). Largely altered 18 metabolites (thrombus/blood ratio: >5 or <0.5) included glycolytic metabolites, redox-related metabolites, purine nucleotides and tryptophan metabolites. Among the metabolites with >5-fold increase, lactic acid was most abundant and guanine modestly enhanced whole blood clotting with thromboelastometry. Lactic acid and adenosine monophosphate inhibited collagen-induced platelet aggregation. Human DVTs were rich in erythrocytes expressing Glut-1. The erythrocyte content and Glut-1 expression were negatively correlated with the time after onset of DVT. CONCLUSIONS: Glycolysis-, purine-, and redox-related metabolites may reflect fresh erythrocyte-rich venous thrombus, and altered metabolites may affect venous thrombus formation. An increased level of lactate may reflect active glycolysis of thrombus cellular components, predominantly erythrocytes.
BACKGROUND: Thrombolytic therapy is effective in fresh deep vein thrombosis (DVT) although the benefit may fall below the risk of bleeding in non-fresh thrombosis. Markers reflecting fresh DVT have not been established. The present study aims to identify metabolites reflecting fresh venous thrombus and their role in thrombus formation. METHODS: Metabolites of rabbit venous blood and jugular venous thrombus 4 h after thrombus induction were analysed using electrophoresis-time of flight mass spectrometry. The effects of the altered metabolites on blood coagulation and platelet aggregation were assessed by using rotation thromboelastometry and platelet aggregometer. Cellular contents and glucose transporter (Glut)-1 expression in aspirated human DVT samples were pathologically analysed. RESULTS: Metabolome analysis identified 226 metabolites (133 cationic and 93 anionic metabolites). Largely altered 18 metabolites (thrombus/blood ratio: >5 or <0.5) included glycolytic metabolites, redox-related metabolites, purine nucleotides and tryptophan metabolites. Among the metabolites with >5-fold increase, lactic acid was most abundant and guanine modestly enhanced whole blood clotting with thromboelastometry. Lactic acid and adenosine monophosphate inhibited collagen-induced platelet aggregation. Human DVTs were rich in erythrocytes expressing Glut-1. The erythrocyte content and Glut-1 expression were negatively correlated with the time after onset of DVT. CONCLUSIONS: Glycolysis-, purine-, and redox-related metabolites may reflect fresh erythrocyte-rich venous thrombus, and altered metabolites may affect venous thrombus formation. An increased level of lactate may reflect active glycolysis of thrombus cellular components, predominantly erythrocytes.
Authors: Kun Yang; Matthew Holt; Min Fan; Victor Lam; Yong Yang; Tuanzhu Ha; David L Williams; Chuanfu Li; Xiaohui Wang Journal: Front Immunol Date: 2022-03-23 Impact factor: 7.561
Authors: David Zaragoza-Huesca; Pedro Garrido-Rodríguez; Paula Jiménez-Fonseca; Eva Martínez de Castro; Manuel Sánchez-Cánovas; Laura Visa; Ana Custodio; Ana Fernández-Montes; Julia Peñas-Martínez; Patricia Morales Del Burgo; Javier Gallego; Ginés Luengo-Gil; Vicente Vicente; Irene Martínez-Martínez; Alberto Carmona-Bayonas Journal: Biomedicines Date: 2022-01-11