HDL in humans with cardiovascular disease exhibits a proteomic signature

BackgroundAlterations 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 HDL2 could be used as biomarkers for coronary artery disease (CAD).MethodsTwenty control and eighteen CAD subjects matched for HDL-cholesterol, age, and sex were studied. HDL2 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.ResultsPartial least squares discriminant analysis (PLS-DA) of mass spectra clearly differentiated CAD from control subjects with area under the receiver operating characteristic curve (ROCAUC) of 0.94. Targeted tandem mass spectrometric analysis of the model's significant features revealed that HDL2 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 (ROCAUC = 0.82).ConclusionsHDL2 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.