on August 25, 2005
Published online before print August 25, 2005, doi: 10.1161/01.ATV.0000183928.25844.f6
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 29, 2005
Accepted on August 15, 2005
Proteomic and Metabolomic Analyses of Atherosclerotic Vessels From Apolipoprotein E-Deficient Mice Reveal Alterations in Inflammation, Oxidative Stress, and Energy Metabolism
Manuel Mayr *;
From the Departments of Cardiac and Vascular Sciences (M.M., U.M., X.Y., L.L., S.F., Y.H., Q.X.) and Basic Medical Sciences (Y.-L.C., H.T., J.R.G.), St George’s, University of London, UK.
* To whom correspondence should be addressed. E-mail: m.mayr{at}sgul.ac.uk.
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.
Methods and 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.
Conclusion--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.
Key words: animal model • apolipoprotein E • atherosclerosis • metabolomics • oxidative stress • proteomics
This article has been cited by other articles:
 |
|
 |
|
  M. Mayr, D. Grainger, U. Mayr, A. S. Leroyer, G. Leseche, A. Sidibe, O. Herbin, X. Yin, A. Gomes, B. Madhu, et al. Proteomics, Metabolomics, and Immunomics on Microparticles Derived From Human Atherosclerotic Plaques Circ Cardiovasc Genet, August 1, 2009; 2(4): 379 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mayr Metabolomics: Ready for the Prime Time? Circ Cardiovasc Genet, October 1, 2008; 1(1): 58 - 65. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kisucka, A. K. Chauhan, I. S. Patten, A. Yesilaltay, C. Neumann, R. A. Van Etten, M. Krieger, and D. D. Wagner Peroxiredoxin1 Prevents Excessive Endothelial Activation and Early Atherosclerosis Circ. Res., September 12, 2008; 103(6): 598 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Smith, E. C. Smith, M. L. Gilman, J. L. Anderson, and R. L. Taylor Jr. Differentially Expressed Soluble Proteins in Aortic Cells from Atherosclerosis-Susceptible and Resistant Pigeons Poult. Sci., July 1, 2008; 87(7): 1328 - 1334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mayr, A. Zampetaki, A. Sidibe, U. Mayr, X. Yin, A. I. De Souza, Y.-L. Chung, B. Madhu, P. H. Quax, Y. Hu, et al. Proteomic and Metabolomic Analysis of Smooth Muscle Cells Derived From the Arterial Media and Adventitial Progenitors of Apolipoprotein E-Deficient Mice Circ. Res., May 9, 2008; 102(9): 1046 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mayr, A. Sidibe, and A. Zampetaki The Paradox of Hypoxic and Oxidative Stress in Atherosclerosis J. Am. Coll. Cardiol., April 1, 2008; 51(13): 1266 - 1267. [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Miller, W. C. Watson, K. A. Kerr, C. A. Labarrere, N. X. Chen, M. A. Deeg, and J. L. Unthank Development of progressive aortic vasculopathy in a rat model of aging Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2634 - H2643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Drake and P. Ping Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Proteomics approaches to the systems biology of cardiovascular diseases J. Lipid Res., January 1, 2007; 48(1): 1 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mayr, J. Zhang, A. S. Greene, D. Gutterman, J. Perloff, and P. Ping Proteomics-based Development of Biomarkers in Cardiovascular Disease: Mechanistic, Clinical, and Therapeutic Insights Mol. Cell. Proteomics, October 1, 2006; 5(10): 1853 - 1864. [Full Text] [PDF]
|
|