Plasma Biomarkers and Identification of Resilient Metabolic Disruptions in Patients With Venous Thromboembolism Using a Metabolic Systems Approach. Issue 10 (October 2020)

• Record Type: Journal Article
• Authors: Fraser, Karl; Roy, Nicole C.; Goumidi, Louisa; Verdu, Alexandre; Suchon, Pierre; Leal-Valentim, Felipe; Trégouët, David-Alexandre; Morange, Pierre-Emmanuel; Martin, Jean-Charles
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 40:Issue 10(2020)
• Publication Date: 2020-10
• Subjects: fasting -- metabolic networks -- metabolomics -- pulmonary embolism -- trimethylamine N-oxide -- venous thromboembolism; Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.120.314480
• Languages: English
• ISSNs: 1079-5642

Abstract

Abstract : Objective: Deep vein thrombosis and pulmonary embolism referred as venous thromboembolism (VTE) are a common cause of morbidity and mortality. Plasma from healthy controls or individuals who have experienced a VTE were analyzed using metabolomics to characterize biomarkers and metabolic systems of patients with VTE. Approach and Results: Polar metabolite and lipidomic profiles from plasma collected 3 months after an incident VTE were obtained using liquid chromatography mass spectrometry. Fasting-state plasma samples from 42 patients with VTE and 42 healthy controls were measured. Plasma metabolomic profiling identified 512 metabolites forming 62 biological clusters. Multivariate analysis revealed a panel of 21 metabolites altogether capable of predicting VTE status with an area under the curve of 0.92 ( P =0.00174, selectivity=0.857, sensitivity=0.971). Multiblock systems analysis revealed 25 of the 62 functional biological groups as significantly affected in the VTE group ( P <0.05 to control). Complementary correlation network analysis of the dysregulated functions highlighted a subset of the lipidome composed mainly of n-3 long-chain polyunsaturated fatty acids within the predominant triglycerides as a potential regulator of the post-VTE event biological response, possibly controlling oxidative and inflammatory defence systems, and metabolic disorder associated dysregulations. Of interest was microbiota metabolites including trimethylamine N-oxide that remained associated to post incident VTE patients, highlighting a possible involvement of gut microbiota on VTE risk and relapse. Conclusions: These findings show promise for the elucidation of underlying mechanisms and the design of a diagnostic test to assess the likely efficacy of clinical care in patients with VTE. Abstract : Supplemental Digital Content is available in the text.