4.7 Review

Application of Metabolic Profiling to Abdominal Aortic Aneurysm Research

Journal

JOURNAL OF PROTEOME RESEARCH
Volume 16, Issue 7, Pages 2325-2332

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.6b00894

Keywords

aneurysm; metabonomics; metabolomics; metabolic profiling; systems biology; arterial disease

Funding

  1. National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London [P37560]
  2. Circulation Foundation [P46379]
  3. Graham-Dixon Charitable Trust [P56657]
  4. Royal College of Surgeons/Dunhill Medical Trust Two Year Fellowship [P52664]
  5. Rosetrees Trust [P50472]
  6. Mason Medical Research Trust [P56662]
  7. Imperial Private Healthcare [P60220]

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Abdominal aortic aneurysm (AAA) is a complex disease posing diagnostic and therapeutic challenges. Metabonomics may aid in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis. A systematic review of the diversity and outcomes of existing AAA metabonomic research has been performed. Original research studies applying metabonomics to human aneurysmal disease are included. Seven relevant articles were identified: four studies were based on plasma/serum metabolite profiling, and three studies examined aneurysmal tissue. Aminomalonic acid, guanidinosuccinic acid; and glycerol emerge as potential plasma biomarkers of large aneurysm. Lipid profiling improves predictive models of aneurysm presence. Patterns of metabolite variation associated with AAA relate to carbohydrate and lipid metabolism. Perioperative perturbations in metabolites suggest differential systemic inflammatory responses to surgery, generating hypotheses for adjunctive perioperative therapy. Significant limitations include small study sizes, lack of correction for multiple testing false discovery rates, and single time-point sampling. Metabolic profiling carries the potential to identify biomarkers of AAA and elucidate pathways underlying aneurysmal disease. Statistically and methodologically robust studies are required for validation, addressing the hiatus in understanding mechanisms of aneurysm growth and developing effective treatment strategies.

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