Abstract 182: Quantitative Proteomics Reveals Dynamic Changes of Plasma Proteome in APOE-Deficient Mice at Four Phases of Atherosclerosis
Introduction To understand the mechanism for atherosclerotic disease at molecular level, we analyzed the dynamic changes of plasma proteome in mice at four different disease stages vs. control based on hypothesis that a panel of plasma proteins might associate with the progression of atherosclerosis.
Methods Male APOE knockout (-/-) mice were fed with high fat diet and euthanized at 8, 12, 18 or 24 weeks of age, representing the early, intermediate, moderate and later stages of disease. Age-matched male wild type mice fed with high fat diet served as controls. At the time of euthanasia, aorta and plasma were collected. A mass spectrometry-based proteomics approach was employed to simultaneously quantify proteins in eight pooled samples.
Results Image analysis of lesions in aortas (stained with Sudan IV) from 40 APOE -/- mice (10 mice at each time point) demonstrated the development of four different phases of disease (Fig.). No lesion was observed in the control mice. We have identified 57 dysregulated proteins (e.g., fibrinogen beta and gamma chains, complement C3, C4B, C9, apolipoproteins, etc.) at four disease stages. These protein’s expression levels, biological functions (e.g. immune modulation and inflammation), and pathways (e.g., complement and cogulation cascades) provide a better understanding of the basic molecular processes in atherosclerosis.
Conclusions 1) Proteomics analysis of plasma proteome changes at different stages of APOE-deficient mice facilitated the mechanistic studies of atherosclerosis. 2) A panel of plasma proteins was identified as potential “signatures” of atherosclerosis which may help early diagnosis and therapeutic intervention.
- © 2013 by American Heart Association, Inc.