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HDL in humans with cardiovascular disease exhibits a proteomic signature.

ABSTRACT: 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.

SUBMITTER: Vaisar T

PROVIDER: S-EPMC2862883 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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HDL in humans with cardiovascular disease exhibits a proteomic signature.

Vaisar Tomás T Mayer Philip P Nilsson Erik E Zhao Xue-Qiao XQ Knopp Robert R Prazen Bryan J BJ

Clinica chimica acta; international journal of clinical chemistry 20100320 13-14

<h4>Background</h4>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).<h4>Methods</h4>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 matri ...[more]

PMID: 20307520

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Project description:Background The previous study investigated whether the functions of small, medium, and large high density lipoprotein (S/M/L-HDL) are correlated with protein changes in mice. Herein, the proteomic and functional analyses of high density lipoprotein (HDL) subclasses were performed in humans and rats. Methods After purifying S/M/L-HDL subclasses from healthy humans (n = 6) and rats (n = 3) using fast protein liquid chromatography (FPLC) with calcium silica hydrate (CSH) resin, the proteomic analysis by mass spectrometry was conducted, as well as the capacities of cholesterol efflux and antioxidation was measured. Results Of the 120 and 106 HDL proteins identified, 85 and 68 proteins were significantly changed in concentration among the S/M/L-HDL subclasses in humans and rats, respectively. Interestingly, it was found that the relatively abundant proteins in the small HDL (S-HDL) and large HDL (L-HDL) subclasses did not overlap, both in humans and in rats. Next, by searching for the biological functions of the relatively abundant proteins in the HDL subclasses via Gene Ontology, it was displayed that the relatively abundant proteins involved in lipid metabolism and antioxidation were enriched more in the medium HDL (M-HDL) subclass than in the S/L-HDL subclasses in humans, whereas in rats, the relatively abundant proteins associated with lipid metabolism and anti-oxidation were enriched in M/L-HDL and S/M-HDL, respectively. Finally, it was confirmed that M-HDL and L-HDL had the highest cholesterol efflux capacity among the three HDL subclasses in humans and rats, respectively; moreover, M-HDL exhibited higher antioxidative capacity than S-HDL in both humans and rats. Conclusions The S-HDL and L-HDL subclasses are likely to have different proteomic components during HDL maturation, and results from the proteomics-based comparison of the HDL subclasses may explain the associated differences in function. Supplementary Information The online version contains supplementary material available at 10.1186/s12944-023-01829-9.

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HDL in humans with cardiovascular disease exhibits a proteomic signature.

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HDL in humans with cardiovascular disease exhibits a proteomic signature.

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