Proteomic Analysis of Defined HDL Subpopulations Reveals Particle-Specific Protein Clusters: Relevance to Antioxidative Function
Open accessAbstract
Objective— Recent proteomic studies have identified multiple proteins that coisolate with human HDL. We hypothesized that distinct clusters of protein components may distinguish between physicochemically-defined subpopulations of HDL particles, and that such clusters may exert specific biological function(s). Methods and Results— We investigated the distribution of proteins across 5 physicochemically-defined particle subpopulations of normolipidemic human HDL (HDL2b, 2a, 3a, 3b, 3c) fractionated by isopycnic density gradient ultracentrifugation. Liquid chromatography/electrospray mass spectrometry identified a total of 28 distinct HDL-associated proteins. Using an abundance pattern analysis of peptide counts across the HDL subfractions, these proteins could be grouped into 5 distinct classes. A more in-depth correlational network analysis suggested the existence of distinct protein clusters, particularly in the dense HDL3 particles. Levels of specific HDL proteins, primarily apoL-I, PON1, and PON3, correlated with the potent capacity of HDL3 to protect LDL from oxidation. Conclusions— These findings suggest that HDL is composed of distinct particles containing unique (apolipo)protein complements. Such subspeciation forms a potential basis for understanding the numerous observed functions of HDL. Further work using additional separation techniques will be required to define these species in more detail.
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Unlike HDL from healthy subjects, HDL from patients with CHD, kidney disease or diabetes mellitus have no protective vascular effects or may even cause paradoxical harmful effects.
“Unlike HDL from healthy subjects, HDL from patients with CHD, kidney disease or diabetes mellitus have no protective vascular effects or may even cause paradoxical harmful effects [55, 56, 61, 70, 71, 75, 76].”
From HDL cholesterol: reappraisal of its clinical relevance (2017) · cites this paper as [55]
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- Authors
- Davidson, W. S., Silva, R. A. G. D., Chantepie, S., Lagor, W. R., Chapman, M. J., & Kontush, A.
- Affiliations
- Inserm (FR)
- Corresponding author
- Davidson, W. Sean
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2009-06
- Volume
- 29
- Issue
- 6
- Pages
- 870-876
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC2845307
- OpenAlex
- W2128633067
- Cited by
- 415
- References
- 40
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 12 · 2023: 22 · 2022: 20 · 2021: 27 · 2020: 24 · 2019: 20 · 2018: 20 · 2017: 28 · 2016: 22 · 2015: 37 · 2014: 39 · 2013: 44 · 2012: 28
- FWCI
- 26.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pfizer
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL067093, HL-67093)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- HDL subpopulations, HDL proteome, HDL-associated proteins, HDL3, HDL2, HDL3b, HDL2b, HDL2a, protein clusters, paraoxonase 1, PON3, protein-protein interaction network
- MeSH terms
- Apolipoprotein L1, Antioxidants, Apolipoproteins, Centrifugation, Isopycnic, Chromatography, Liquid, Esterases, Humans, Lipoproteins, HDL, Male, Protein Binding, Spectrometry, Mass, Electrospray Ionization, Proteomics, Aryldialkylphosphatase, Lipoproteins, HDL2, Lipoproteins, HDL3
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