HDL in humans with cardiovascular disease exhibits a proteomic signature

• 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
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2010.03.023

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.