cvd-logocvd - Study ID Exp21681990b

PubMed ID21681990
AuthorsJing L(1), Parker CE, Seo D, Hines MW, Dicheva N, Yu Y, Schwinn D, Ginsburg GS, Chen X.
TitleDiscovery of biomarker candidates for coronary artery disease from an APOE-knock out mouse model using iTRAQ-based multiplex quantitative proteomics.
JournalProteomics. 2011 Jul;11(14):2763-76.
AbstractDue 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 12?wk 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 gamma and beta 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.

Sample characteristics

SpeciesTissue / SourceCompartmentDiseaseNDetection methodSample
Mus musculusbloodplasmaCAD6MALDI-TOF/TOFDem21681990a, Dem21681990b

Sample description and preparation

N (case)3
N (control)3
Disease (case)APOE-knock out Coronary artery disease (CAD) progression model
Disease (control)wild-type
Disease inductionapolipoprotein E knockout (APOE(-/-) ), 12 weeks
Preparation specific methodiTRAQ-labelling
Separation2D-LC
Storage condition-80C

Sample analysis

Software analysis toolProteinPilot 2.0.1
Software thresholdP<0.05

Molecule list

Molecule IDextExternal IDGeneNameSource accRegulation (case/control)Scores
A5625 A1AG1_HUMANORM1, AGP1, ORM2Alpha-1-acid glycoprotein 1 precursorQ60590ratio: 1.700
A5626XA1AG2_HUMANORM2, AGP2, AGP-BAlpha-1-acid glycoprotein 2 precursorP07361ratio: 2.100
A8373 A1AT5_MOUSESerpina1e,Dom5,Spi1-5Alpha-1-antitrypsin 1-5Q00898ratio: 2.600
A8783XFETUA_HUMANAHSG, FETUA, PRO2743Alpha-2-HS-glycoprotein precursorP29699ratio: 1.300
A810BXAPOA4_HUMANAPOA4, ApoA-IV, APOA-IVApolipoprotein A-IV precursorP06728ratio: 1.700
A8663 APOH_HUMANAPOH, B2G1Beta-2-glycoprotein 1 precursorQ01339ratio: 1.500
A1540XFA9_HUMANF9, FIX, F9p22Coagulation factor IX precursorP16294ratio: 1.400
A1708XC1QC_HUMANC1QC, C1QGComplement C1q subcomponent, C chain precursorQ02105ratio: 1.500
A1616XCO5_HUMANC5, CPAMD4Complement C5 precursorP06684ratio: 1.200
A1625XCO8A_HUMANC8AComplement component C8 alpha chain precursorQ8K182ratio: 1.700
A1626XCO8B_HUMANC8BComplement component C8 beta chain precursorQ8BH35ratio: 1.300
A1627XCO8G_HUMANC8GComplement component C8 gamma chain precursorQ8VCG4ratio: 1.500
A0156 EGFR_HUMANEGFR, ERBB, ERBB1Epidermal growth factor receptor precursorQ01279ratio: 1.500
A1493XFIBB_HUMANFGBFibrinogen beta chain precursorQ8K0E8ratio: 1.600
A1494XFIBG_HUMANFGG, PRO2061Fibrinogen gamma chain precursorQ8VCM7ratio: 1.800
A1631XHPT_HUMANHPHaptoglobin precursorQ61646ratio: 3.300
A021CXHEMO_HUMANHPXHemopexin precursorQ91X72ratio: 1.500
A8363XIGHM_HUMANIGHM, IgIg mu chain CP01873ratio: 3.500
A1712 TRFL_HUMANLTF, LF, GIG12Lactotransferrin precursorP08071ratio: 2.200
A150C MUP1_MOUSEMup1Major urinary protein 1P11588ratio: 2.000
A8954XPROP_HUMANCFP, PFCComplement factor ProperdinP11680ratio: 1.500
A1469 THRB_HUMANF2Prothrombin precursorP19221ratio: 1.300
A806H PHAX_HUMANPHAX, RNUXARNA U small nuclear RNA export adapter proteinQ9JJT9ratio: 1.600
A8494 SPA3N_MOUSESerpina3n,Spi2Serine (or cysteine) peptidase inhibitor, clade A, member 3NQ91WP6ratio: 1.600
A643CXTRFE_HUMANTF, PRO1400Serotransferrin precursorQ921I1ratio: 2.700
A1597XSAMP_HUMANAPCS, PTX2Serum amyloid P-component precursorP12246ratio: 2.800
A8967 PSMD2_HUMANPSMD2, TRAP226S proteasome non-ATPase regulatory subunit 2Q8VDM4ratio: 0.530
A1552XAPOA1_HUMANAPOA1, A175PApolipoprotein A-I precursorQ00623ratio: 0.310
A809BXAPOA2_HUMANAPOA2Apolipoprotein A-II precursorP09813ratio: 0.170
A1809 APOC2_HUMANAPOC2, APC2Apolipoprotein C-II precursorQ05020ratio: 0.310
A813BXAPOC3_HUMANAPOC3Apolipoprotein C-III precursorP33622ratio: 0.440
A815BXAPOD_HUMANAPODApolipoprotein D precursorP51910ratio: 0.370
A1176XAPOE_HUMANAPOEApolipoprotein E precursorP08226ratio: 0.060
A1819 B2MG_HUMANB2M, HDCMA22PBeta-2-microglobulin precursorP01887ratio: 0.540
A5964 CAH2_HUMANCA2Carbonic anhydrase 2P00920ratio: 0.350
A1598XCO3_HUMANC3, CPAMD1Complement C3 precursorP01027ratio: 0.680
A8721XCO4B_HUMANC4B, C4B12, C4B-1Complement C4-B precursorP01029ratio: 0.640
A1602XCFAB_HUMANCFB, BF, BFDComplement factor B precursorP04186ratio: 0.830
A0133 DYHC1_HUMANDYNC1H1, Dnchc1, DHC1Dynein heavy chain, cytosolicQ9JHU4ratio: 0.300
A106B TF3C1_HUMANGTF3C1, A-670B5, A-951C1A1General transcription factor 3C polypeptide 1Q8K284ratio: 0.500
A7382 PGTA_HUMANRABGGTAGeranylgeranyl transferase type-2 subunit alphaQ9JHK4ratio: 0.160
A1821 1A25_HUMANHLA-A, HLA-A*24, HLAHLA class I histocompatibility antigen, A-2 alpha chain precursorP01898ratio: 0.330
A0146 HSP7C_HUMANHSPA8, HSC70, HSP73Heat shock cognate 71 kDa proteinP63017ratio: 0.710
A1741XHBA_HUMANHBA1, HBA2, HBZHemoglobin subunit alphaP01942ratio: 0.320
A016C HBB1_MOUSEHbb-b1,Hbbt1Hemoglobin subunit beta-1P02088ratio: 0.260
A8431 ITIH1_HUMANITIH1, IGHEP1, PRO2769Inter-alpha (globulin) inhibitor H1Q61702ratio: 0.790
A8432XITIH2_HUMANITIH2, IGHEP2Inter-alpha-trypsin inhibitor heavy chain H2 precursorQ61703ratio: 0.620
A9356 IL1AP_HUMANIL1RAP, IL1R3Interleukin-1 receptor accessory protein precursorQ61730ratio: 0.750
A409J B5MCL0 Putative uncharacterized protein ENSP00000385074P39039ratio: 0.730
A0372XPRDX2_HUMANPRDX2, NKEFB, TDPX1Peroxiredoxin 2Q61171ratio: 0.340
A7386XPHLD_HUMANGPLD1, PIGPLD1, GPIPLDMPhosphatidylinositol-glycan-specific phospholipase D 1 precursorO70362ratio: 0.630
A1591 IC1_HUMANSERPING1, C1IN, C1NHSerine/cysteine proteinase inhibitor clade G member 1P97290ratio: 0.700
A343E SPP24_HUMANSPP2, SPP24Secreted phosphoprotein 24 precursorQ8K1I3ratio: 0.670
A5592XSAA4_HUMANSAA4, CSAASerum amyloid A-4 proteinP31532ratio: 0.490
A7457XPON1_HUMANPON1, PONParaoxonase 1P52430ratio: 0.510

Compile date 02-09-2018© C/VD project