Abstract
Deep vein thrombosis (DVT) and pulmonary embolism (PE) have high morbidity, reduce quality of life, and can cause death. Biomarkers or genetic risk factors have not been identified in patients with DVT. In present study, serum of 61 patients suffering from DVT and a rat DVT model (n = 10) were assayed by a proton nuclear magnetic resonance (1H NMR) metabolomics technique combing with multivariate statistical analysis to identify the metabolites. The MetPA platform was used to identify differences in the metabolic pathways between the rat model and patients. The metabolomics results discovered that 11 different metabolites in rats and 20 different metabolites in DVT patients. Seven metabolites both altered in the rats and patients. Moreover, we observed changes in the metabolic pathways, including carbohydrate metabolism, lipid metabolism, and amino acid metabolism that were induced immediately by the thrombosis. Pathway of aminoacyl-tRNA biosynthesis perturbed only in the patients which was associated with the genetic risk factor of DVT. The study demonstrated that serum 1H NMR metabolomics can be used to diagnose DVT in the clinic. The altered pathways related to thrombosis and genetics will provide a foundation and new strategies for understanding the pathological mechanism and pharmacological targets of DVT.
Highlights
Deep vein thrombosis (DVT) is a condition in which a blood clot forms in a deep vein, most commonly in the lower extremities
Due to the complexity of the pathogenesis and diagnosis, novel diagnostic and prognostic biomarkers are needed for suspected patients as well as for early diagnosis and timely treatment
The results showed differences in metabolites and pathways between the rat model and the DVT patients, indicating the feasibility of metabolomics for discriminating DVT disease
Summary
Deep vein thrombosis (DVT) is a condition in which a blood clot forms in a deep vein, most commonly in the lower extremities. The main inherited thrombophilias include plasma deficiencies of natural anticoagulants antithrombin and proteins C and S; the gain-of-function mutations factor V Leiden and prothrombin G20210A; some dysfibrinogenemias, and high plasma levels of coagulation factor VIII8,9. According to these genetic risk factors, only about 40% of all previously unexplained episodes of venous thromboembolism (VTE) can be explained. As an important component of systems biology, metabolomics has been widely applied to study diagnostic and prognostic biomarkers related to disease and the pathogenesis of disease by detecting endogenous small compounds in biological samples[13]. The potential genetic risk factors related to metabolites, genes, or transcription could explain the mechanism of complex diseases, such as DVT
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