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Updated: Sep 14, 2025

Deep Proteome Profiling by Isobaric Labeling, Extensive Liquid Chromatography, Mass Spectrometry, and Software-assisted Quantification
Published on: November 15, 2017
HDL proteome: from its characterization to quantitative measurements in particle subspecies and functional
Tomáš Vaisar1, Graziella Eliza Ronsein2
1Diabetes Institute, School of Medicine, University of Washington, Seattle, WA, USA.
Insights
Recent high-density lipoprotein cholesterol (HDL-C) therapeutic failures highlight the need to understand HDL. The HDL proteome
Area of Science:
- Lipidomics and Proteomics
- Cardiovascular Research
- Biochemistry
Background:
- High-density lipoprotein cholesterol (HDL-C) therapies have faced recent setbacks, necessitating a re-evaluation of HDL's role.
- The HDL proteome, comprising over 50% of HDL mass, is crucial for its diverse functions.
- HDL's significant heterogeneity requires advanced methods for characterizing its subspecies and functions.
Purpose of the Study:
- To review recent advancements in HDL proteome research, focusing on mass spectrometry-based proteomics.
- To emphasize the importance of studying HDL heterogeneity and its functional implications.
- To highlight the need for harmonized methodologies in isolating and quantifying HDL subspecies and their proteomes.
Main Methods:
- Literature review of studies on HDL proteomes published in the last five years.
- Focus on mass spectrometry-based proteomics applied to HDL analysis.
- Examination of studies investigating HDL heterogeneity, subspecies, and function.
Main Results:
- The HDL proteome is intrinsically linked to HDL function.
- Recent proteomic approaches offer new ways to study HDL subspecies.
- Standardization in isolation and quantification is essential for advancing HDL research.
Conclusions:
- Understanding the HDL proteome is critical for deciphering HDL's structure-function relationship.
- New approaches to isolate HDL subspecies and quantify their proteomes are needed.
- Harmonized methodologies will enable new insights into HDL's role in disease pathology and potential therapeutic targets.
Introduction:
Recent failures of therapeutic interventions aimed at elevating high-density lipoprotein cholesterol (HDL-C) have renewed the need to reconceptualize HDL. The HDL proteome constitutes over 50% of the HDL mass and it is the richest among lipoproteins. HDL is also the most heterogeneous lipoprotein, and unraveling the determinants of its pleiotropic functions requires new approaches to characterize HDL subspecies as well as harmonization of isolation and quantification methodologies.
Areas Covered:
We have reviewed studies focusing on HDL proteomes from the past 5 years, with particular focus on recent developments in mass spectrometry-based proteomics applied to HDL, and the studies of HDL heterogeneity and function. Emphasis is also given on the quantification of the proteome of HDL-specific subspecies and on the studies relating the HDL proteome to its function. We further discuss the need for harmonization in HDL subpopulations and subspecies isolation and in proteome quantification.
Expert Opinion:
The HDL proteome is undisputedly related to the HDL function. The development of new approaches to isolate HDL subspecies, together with the implementation of consistent quantification strategies, is needed to provide new insights into the structure-function relationship of HDL particles, unravel the role of HDL in the pathology of diseases, and provide new metrics of HDL.

