title: Proteomic and metabolomic analyses of atherosclerotic vessels from apolipoprotein E-deficient mice reveal alterations in inflammation, oxidative stress, and energy metabolism.
abstract: OBJECTIVE
  Proteomics and metabolomics are emerging technologies to study molecular mechanisms of diseases. We applied these techniques to identify protein and metabolite changes in vessels of apolipoprotein E(-/-) mice on normal chow diet.
  
  
  RESULTS
  Using 2-dimensional gel electrophoresis and mass spectrometry, we identified 79 protein species that were altered during various stages of atherogenesis. Immunoglobulin deposition, redox imbalance, and impaired energy metabolism preceded lesion formation in apolipoprotein E(-/-) mice. Oxidative stress in the vasculature was reflected by the oxidation status of 1-Cys peroxiredoxin and correlated to the extent of lesion formation in 12-month-old apolipoprotein E(-/-) mice. Nuclear magnetic resonance spectroscopy revealed a decline in alanine and a depletion of the adenosine nucleotide pool in vessels of 10-week-old apolipoprotein E(-/-) mice. Attenuation of lesion formation was associated with alterations of NADPH generating malic enzyme, which provides reducing equivalents for lipid synthesis and glutathione recycling, and successful replenishment of the vascular energy pool.
  
  
  CONCLUSIONS
  Our study provides the most comprehensive dataset of protein and metabolite changes during atherogenesis published so far and highlights potential associations of immune-inflammatory responses, oxidative stress, and energy metabolism.
authors.affiliation: Department of Cardiac and Vascular Sciences, St George's University of London, UK. m.mayr@sgul.ac.uk
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
authors.forename: Yuen-Li
authors.initials: YL
authors.lastname: Chung
authors.forename: Ursula
authors.initials: U
authors.lastname: Mayr
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Yin
authors.forename: Lucy
authors.initials: L
authors.lastname: Ly
authors.forename: Helen
authors.initials: H
authors.lastname: Troy
authors.forename: Salim
authors.initials: S
authors.lastname: Fredericks
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Hu
authors.forename: John R
authors.initials: JR
authors.lastname: Griffiths
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000276:immunology / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers; D015180:Electrophoresis, Gel, Two-Dimensional; D004734:Energy Metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018384:Oxidative Stress / Q000502:physiology; D010088:Oxidoreductases / Q000378:metabolism; D040901:Proteomics; D014657:Vasculitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D015415:Biomarkers; D010088:Oxidoreductases