Integrated proteomic and metabolomic profiling of lymph after trauma-induced hypercoagulopathy and antithrombotic therapy

Abstract

Routine coagulation tests are not widely accepted diagnostic criteria of trauma-induced hypercoagulopathy (TIH) due to insensitivity. Lymphatic vessels drain approximately 10% of the interstitial fluid into the lymphatic system and form lymph. The purpose of this study was to identify the potential lymph biomarkers for TIH. Eighteen male Sprague-Dawley rats were randomly assigned to the sham (non-fractured rats with sham surgery and vehicle treatment), the VEH (fractured rats with vehicle treatment) and the CLO (fractured rats with clopidogrel treatment) group. Thoracic duct lymph was obtained to perform proteomics and untargeted metabolomics. A total of 1207 proteins and 16,695 metabolites were identified. The top 5 GO terms of lymph proteomics indicated that oxidative stress and innate immunity were closely associated with TIH and antithrombotic therapy. The top 5 GO terms of lymph metabolomics showed that homocystine and lysophosphatidylcholine were the differential expressed metabolites (DEMs) between the sham and VEH groups, while cholic acid, docosahexaenoic acid, N1-Methyl-2-pyridone-5-carboxamide, isoleucine and testosterone are the DEMs between the VEH and CLO group. This study presents the first proteomic and metabolomic profiling of lymph after TIH and antithrombotic therapy, and predicts the possible lymph biomarkers for TIH.