HDL in humans with cardiovascular disease exhibits a proteomic signature

Alterations in protein composition and oxidative damage of high density lipoprotein (HDL) have been proposed to impair the cardioprotective properties of HDL. We tested whether relative levels of proteins in HDL 2 could be used as biomarkers for coronary artery disease (CAD). Twenty control and eigh...

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Bibliographic Details
Published in:Clinica chimica acta 2010-07, Vol.411 (13), p.972-979
Main Authors: Vaisar, Tomáš, Mayer, Philip, Nilsson, Erik, Zhao, Xue-Qiao, Knopp, Robert, Prazen, Bryan J.
Format: Article
Language:English
Subjects:
Biomarkers - metabolism
Cardiovascular risk score
Case-Control Studies
Chromatography, Liquid
Coronary Artery Disease - metabolism
Female
Humans
Inflammation
Lipoproteins, HDL - metabolism
Male
Mass spectrometry
Middle Aged
Oxidized HDL
Partial least squares discriminant analysis
Pattern Recognition, Automated
Proteomics
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Tandem Mass Spectrometry
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Summary:Alterations in protein composition and oxidative damage of high density lipoprotein (HDL) have been proposed to impair the cardioprotective properties of HDL. We tested whether relative levels of proteins in HDL 2 could be used as biomarkers for coronary artery disease (CAD). Twenty control and eighteen CAD subjects matched for HDL-cholesterol, age, and sex were studied. HDL 2 isolated from plasma was digested with trypsin and analyzed by high-resolution matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and pattern recognition analysis. Partial least squares discriminant analysis (PLS-DA) of mass spectra clearly differentiated CAD from control subjects with area under the receiver operating characteristic curve (ROC AUC) of 0.94. Targeted tandem mass spectrometric analysis of the model's significant features revealed that HDL 2 of CAD subjects contained oxidized methionine residues of apolipoprotein A-I and elevated levels of apolipoprotein C-III. A proteomic signature composed of MALDI-MS signals from apoA-I, apoC-III, Lp(a) and apoC-I accurately classified CAD and control subjects (ROC AUC = 0.82). HDL 2 of CAD subjects carries a distinct protein cargo and that protein oxidation helps generate dysfunctional HDL. Moreover, models based on selected identified peptides in MALDI-TOF mass spectra of the HDL may have diagnostic potential.
ISSN:0009-8981
1873-3492
DOI:10.1016/j.cca.2010.03.023