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Isolation, Characterization, and Proteomic Analysis of Plasma-Derived Extracellular Vesicles for Cardiovascular Biomarker Discovery
05:30

Isolation, Characterization, and Proteomic Analysis of Plasma-Derived Extracellular Vesicles for Cardiovascular Biomarker Discovery

Published on: January 31, 2025

HDL in humans with cardiovascular disease exhibits a proteomic signature

Tomás Vaisar1, Philip Mayer, Erik Nilsson

  • 1Department of Medicine, School of Medicine, University of Washington, Seattle, Washington 98195, USA. tvaisar@u.washington.edu

Clinica Chimica Acta; International Journal of Clinical Chemistry
|March 24, 2010
PubMed

Insights

High-density lipoprotein (HDL) protein changes, including oxidation, indicate coronary artery disease (CAD). HDL(2) protein profiles show potential as novel biomarkers for diagnosing CAD.

Area of Science:

  • Cardiovascular proteomics
  • Biomarker discovery
  • Mass spectrometry in disease diagnostics

Background:

  • High-density lipoprotein (HDL) cardioprotective functions may be compromised by altered protein composition and oxidative damage.
  • Investigating HDL(2) protein levels as potential biomarkers for coronary artery disease (CAD) is crucial.

Purpose of the Study:

  • To determine if relative protein levels in HDL(2) can serve as biomarkers for coronary artery disease (CAD).
  • To explore the role of protein oxidation in generating dysfunctional HDL.

Main Methods:

  • Analysis of HDL(2) from 20 control and 18 CAD subjects using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS).
  • Application of pattern recognition analysis, including partial least squares discriminant analysis (PLS-DA).
  • Targeted tandem mass spectrometry to identify specific protein modifications and levels.

Main Results:

  • PLS-DA models differentiated CAD from control subjects with high accuracy (ROC(AUC)=0.94).
  • CAD subjects' HDL(2) showed oxidized apolipoprotein A-I (apoA-I) and elevated apolipoprotein C-III (apoC-III).
  • A proteomic signature including apoA-I, apoC-III, Lp(a), and apoC-I accurately classified subjects (ROC(AUC)=0.82).

Conclusions:

  • HDL(2) in CAD patients possesses a unique protein profile, with oxidation contributing to HDL dysfunction.
  • Proteomic analysis of HDL peptides using MALDI-TOF mass spectrometry shows diagnostic potential for CAD.
Abstract

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