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Proteomic and Metabolomic Analyses of Atherosclerotic Vessels From Apolipoprotein E-Deficient Mice Reveal Alterations in Inflammation, Oxidative Stress, and Energy Metabolism

Proteomic and Metabolomic Analyses of Atherosclerotic Vessels From Apolipoprotein E-Deficient... Atherosclerosis and Lipoprotein Proteomic and Metabolomic Analyses of Atherosclerotic Vessels From Apolipoprotein E–Deficient Mice Reveal Alterations in Inflammation, Oxidative Stress, and Energy Metabolism Manuel Mayr, Yuen-Li Chung, Ursula Mayr, Xiaoke Yin, Lucy Ly, Helen Troy, Salim Fredericks, Yanhua Hu, John R. Griffiths, Qingbo Xu 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 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arteriosclerosis, Thrombosis, and Vascular Biology Wolters Kluwer Health

Proteomic and Metabolomic Analyses of Atherosclerotic Vessels From Apolipoprotein E-Deficient Mice Reveal Alterations in Inflammation, Oxidative Stress, and Energy Metabolism

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References (54)

ISSN
1079-5642
eISSN
1524-4636
DOI
10.1161/01.ATV.0000183928.25844.f6
pmid
16123314
Publisher site
See Article on Publisher Site

Abstract

Atherosclerosis and Lipoprotein Proteomic and Metabolomic Analyses of Atherosclerotic Vessels From Apolipoprotein E–Deficient Mice Reveal Alterations in Inflammation, Oxidative Stress, and Energy Metabolism Manuel Mayr, Yuen-Li Chung, Ursula Mayr, Xiaoke Yin, Lucy Ly, Helen Troy, Salim Fredericks, Yanhua Hu, John R. Griffiths, Qingbo Xu 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

Journal

Arteriosclerosis, Thrombosis, and Vascular BiologyWolters Kluwer Health

Published: Oct 1, 2005

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