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Metabolic Phenotyping in Venous Disease: The Need for Standardization
journal contribution
posted on 2019-10-15, 22:29 authored by Sarah Onida, Matthew K. H. Tan, Marina Kafeza, Richmond T. Bergner, Joseph Shalhoub, Elaine Holmes, Alun H. DaviesVenous thromboembolism (VTE), chronic
venous disease (CVD), and venous leg ulceration (VLU) are clinical
manifestations of a poorly functioning venous system. Though common,
much is unknown of the pathophysiology and progression of these conditions.
Metabolic phenotyping has been employed to explore
mechanistic pathways involved in venous disease. A systematic literature
review was performed: full text, primary research articles on the
applications of nuclear magnetic resonance spectroscopy (NMR) and
mass spectrometry (MS) in human participants and animals were included
for qualitative synthesis. Seventeen studies applying metabolic phenotyping
to venous disease were identified: six on CVD, two on VLU, and nine
on VTE; both animal (n = 6) and human (n = 10) experimental designs were reported, with one study including
both. NMR, MS, and MS imaging were employed to characterize serum,
plasma, urine, wound fluid, and tissue. Metabolites found to be upregulated
in CVD included lipids, branched chain amino acids (BCAA), glutamate,
taurine, lactate, and myo-inositol identified in vein tissue. Upregulated
metabolites in VLU included lactate, BCAA, lysine, 3-hydroxybutyrate,
and glutamate identified in wound fluid and ulcer biopsies. VTE cases
were associated with reduced carnitine levels, upregulated aromatic
amino acids, 3-hydroxybutyrate, BCAA, and lipids in plasma, serum,
thrombus, and vein wall; kynurenine and tricarboxylic acid pathway
dysfunction were reported. Future research should focus on targeted
studies with internal and external validation.