Proteomic analysis of aortae from human lipoprotein(a) transgenic mice shows an early metabolic response independent of atherosclerosis

Rodger, Euan J., Suetani, Rachel J., Jones, Gregory T., Kleffmann, Torsten, Carne, Alan, Legge, Michael and McCormick, Sally P. A. (2012) Proteomic analysis of aortae from human lipoprotein(a) transgenic mice shows an early metabolic response independent of atherosclerosis. PLoS One, 7 1: e30383.1-e30383.9. doi:10.1371/journal.pone.0030383


Author Rodger, Euan J.
Suetani, Rachel J.
Jones, Gregory T.
Kleffmann, Torsten
Carne, Alan
Legge, Michael
McCormick, Sally P. A.
Title Proteomic analysis of aortae from human lipoprotein(a) transgenic mice shows an early metabolic response independent of atherosclerosis
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-01-19
Sub-type Article (original research)
DOI 10.1371/journal.pone.0030383
Open Access Status DOI
Volume 7
Issue 1
Start page e30383.1
End page e30383.9
Total pages 9
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Background: Elevated low density lipoprotein (LDL) and lipoprotein(a) are independent risk factors for the development of atherosclerosis. Using a proteomic approach we aimed to determine early changes in arterial protein expression in transgenic mice containing both human LDL and lipoprotein(a) in circulation.

Methods and Results: Plasma lipid analyses showed the lipoprotein(a) transgenic mice had significantly higher lipid levels than wildtype, including a much increased LDL and high density lipoprotein (HDL) cholesterol. Analysis of aortae from lipoprotein(a) mice showed lipoprotein(a) accumulation but no lipid accumulation or foam cells, leaving the arteries essentially atherosclerosis free. Using two-dimensional gel electrophoresis and mass spectrometry, we identified 34 arterial proteins with significantly altered abundance (P<0.05) in lipoprotein(a) transgenic mice compared to wildtype including 17 that showed a ≥2 fold difference. Some proteins of interest showed a similarly altered abundance at the transcript level. These changes collectively indicated an initial metabolic response that included a down regulation in energy, redox and lipid metabolism proteins and changes in structural proteins at a stage when atherosclerosis had not yet developed.

Conclusions: Our study shows that human LDL and lipoprotein(a) promote changes in the expression of a unique set of arterial proteins which may be early indicators of the metabolic disturbances preceding atherosclerosis.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Mon, 30 Nov 2015, 19:34:37 EST by Rachel Suetani on behalf of Queensland Brain Institute