Summary of Study ST000607

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000444. The data can be accessed directly via it's Project DOI: 10.21228/M8NW2H This work is supported by NIH grant, U2C- DK119886.


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Study IDST000607
Study Title1D-1H-Nuclear Magnetic Resonance Metabolomics Reveals Age-related Changes in Metabolites Associated with Experimental Venous Thrombosis
Study TypeExperimental venous thrombosis
Study SummarySodium heparin preserved whole blood samples were collected from young and old mice with and without induced VT. Samples were subjected to MeOH:CHCl3 extraction and the MeOH was assayed by 1H-NMR. Chenomx software was used for spectral analysis.
University of Michigan
DepartmentClinical Pharmacy
LaboratoryThe NMR Metabolomics Laboratory (Stringer)
Last NameStringer
First NameKathleen
AddressCollege of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109
Submit Date2016-12-08
Num Groups4
Total Subjects31
Raw Data AvailableYes
Raw Data File Type(s)fid
Analysis Type DetailNMR
Release Date2017-07-10
Release Version1
Kathleen Stringer Kathleen Stringer application/zip

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Project ID:PR000444
Project DOI:doi: 10.21228/M8NW2H
Project Title:Metabolomics of Murine Age-related Deep Vein Thrombosis
Project Type:Quantitative 1D-1H-NMR metabolomics
Project Summary:Objective: Age is a significant risk factor for the development of venous thrombosis (VT), but the mechanism(s) that underlie this risk remain(s) undefined and poorly understood. Aging is known to adversely influence inflammation and affect metabolism. Untargeted metabolomics permits an agnostic assessment of the physiological landscape and lends insight into the mechanistic underpinnings of clinical phenotypes. The objective of this exploratory study was to test the feasibility of a metabolomics approach for identifying potential metabolic mechanisms of age-related VT. Methods: We subjected whole blood samples collected from young and old nonthrombosed controls and VT mice 2 days after thrombus induction using the electrolytic inferior vena cava, to a methanol:chloroform extraction and assayed the resulting aqueous fractions using 1D-1H- nuclear magnetic resonance. Normalized mouse metabolite data were compared across groups using analysis of variance (ANOVA) with Holm-Sidak post-testing. In addition, associations between metabolite concentrations and parameters of thrombosis such as thrombus and vein wall weights, and markers of inflammation, vein wall P- and E-selectin levels, were assessed using linear regression. The relatedness of the found significant metabolites was visually assessed using a bioinformatics tool, Metscape, which generates compound-reaction-enzyme-gene networks to aid in the interpretation of metabolomics data. Results: Old mice with VT had a greater mean vein wall weight compared with young mice with VT (P < .05). Clot weight differences between old and young mice followed the same trend as vein wall weight (0.011 % 0.04 g vs 0.008 % 0.003 g; P [ not significant). Glutamine (ANOVA, P < .01), proline (ANOVA, P < .01), and phenylalanine (ANOVA, P <.05) levels were increased in old VT mice compared with age-matched controls and young VT mice. Betaine and/or trimethylamine N-oxide levels were increased in aged mice compared with young animals. Vein wall weight was strongly associated with glutamine (P < .05), and phenylalanine (P <.01) concentrations and there was a trend toward an association with proline (P [ .09) concentration. Vein wall Pselectin, but not E-selectin levels, were increased in old VT mice and were associated with the three found metabolites of age-related VT. Collectively, with the addition of glutamate, these metabolites form a single compound-reaction-enzyme gene network that was generated by Metscape. Conclusions: We used 1D-1H-nuclear magnetic resonance metabolite profiling to identify, for the first time, in an experimental model, three potential metabolites, glutamine, phenylalanine, and proline, associated with age-related VT. These metabolites are metabolically related and their levels are associated with vein wall weight and P-selectin concentrations. In aggregate, these findings provide a “roadmap” of pathways that could be interrogated in future studies, which could include provocation of the glutamine, phenylalanine, and proline pathways in the vein wall. This study introduces metabolomics as a new approach to furthering knowledge about the mechanisms of age-related VT. This study has been published: J Vasc Surg Venous Lymphat Disord. 2016 Apr;4(2):221-30. doi: 10.1016/j.jvsv.2015.09.010. Epub 2015 Nov 24.
Institute:University of Michigan
Department:Department of Surgery
Laboratory:NMR Metabolomics Laboratory, University of Michigan
Last Name:Stringer
First Name:Kathleen
Address:College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109
Funding Source:NIH (DK097153; HL076123), College of Pharmacy Upjohn Award