Discovery of biomarker candidates for coronary artery disease from an APOE-knock out mouse model using iTRAQ-based multiplex quantitative proteomics

Linhong Jing, Carol E. Parker, David M Seo, Maria Warren Hines, Nedyalka Dicheva, Yanbao Yu, Debra Schwinn, Geoffrey S. Ginsburg, Xian Chen

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Due to the lack of precise markers indicative of its occurrence and progression, coronary artery disease (CAD), the most common type of heart diseases, is currently associated with high mortality in the United States. To systemically identify novel protein biomarkers associated with CAD progression for early diagnosis and possible therapeutic intervention, we employed an iTRAQ-based quantitative proteomic approach to analyze the proteome changes in the plasma collected from a pair of wild-type versus apolipoprotein E knockout (APOE-/-) mice which were fed with a high fat diet. In a multiplex manner, iTRAQ serves as the quantitative 'in-spectra' marker for 'cross-sample' comparisons to determine the differentially expressed/secreted proteins caused by APOE knock-out. To obtain the most comprehensive proteomic data sets from this CAD-associated mouse model, we applied both MALDI and ESI-based mass spectrometric (MS) platforms coupled with two different schemes of multidimensional liquid chromatography (2-D LC) separation. We then comparatively analyzed a series of the plasma samples collected at 6 and 12wk of age after the mice were fed with fat diets, where the 6- or 12-wk time point represents the early or intermediate phase of the fat-induced CAD, respectively. We then categorized those proteins showing abundance changes in accordance with APOE depletion. Several proteins such as the γ and β chains of fibrinogen, apolipoprotein B, apolipoprotein C-I, and thrombospondin-4 were among the previously known CAD markers identified by other methods. Our results suggested that these unbiased proteomic methods are both feasible and a practical means of discovering potential biomarkers associated with CAD progression.

Original languageEnglish
Pages (from-to)2763-2776
Number of pages14
JournalProteomics
Volume11
Issue number14
DOIs
StatePublished - Jul 14 2011

Fingerprint

Biomarkers
Knockout Mice
Proteomics
Coronary Artery Disease
Fats
Nutrition
Disease Progression
Apolipoprotein C-I
Proteins
Plasmas
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Apolipoproteins B
High Fat Diet
Apolipoproteins E
Proteome
Liquid Chromatography
Liquid chromatography
Fibrinogen
Early Diagnosis
Heart Diseases

Keywords

  • Animal proteomics
  • Biomarker discovery
  • Coronary artery disease
  • Expression profiling
  • Liquid chromatography-tandem mass spectrometry
  • Quantitative analysis

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Discovery of biomarker candidates for coronary artery disease from an APOE-knock out mouse model using iTRAQ-based multiplex quantitative proteomics. / Jing, Linhong; Parker, Carol E.; Seo, David M; Hines, Maria Warren; Dicheva, Nedyalka; Yu, Yanbao; Schwinn, Debra; Ginsburg, Geoffrey S.; Chen, Xian.

In: Proteomics, Vol. 11, No. 14, 14.07.2011, p. 2763-2776.

Research output: Contribution to journalArticle

Jing, Linhong ; Parker, Carol E. ; Seo, David M ; Hines, Maria Warren ; Dicheva, Nedyalka ; Yu, Yanbao ; Schwinn, Debra ; Ginsburg, Geoffrey S. ; Chen, Xian. / Discovery of biomarker candidates for coronary artery disease from an APOE-knock out mouse model using iTRAQ-based multiplex quantitative proteomics. In: Proteomics. 2011 ; Vol. 11, No. 14. pp. 2763-2776.
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