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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:870.)
© 2009 American Heart Association, Inc.

Cell Biology/Signaling

Proteomic Analysis of Defined HDL Subpopulations Reveals Particle-Specific Protein Clusters

Relevance to Antioxidative Function

W. Sean Davidson; R.A. Gangani D. Silva; Sandrine Chantepie; William R. Lagor; M. John Chapman; Anatol Kontush

From the Department of Pathobiology and Laboratory Medicine (W.S.D., R.A.G.D.S.), University of Cincinnati, Ohio; Université Pierre et Marie Curie-Paris 6 (S.C., M.J.C., A.K.), Paris, France; AP-HP (S.C., M.J.C., A.K.), Groupe hospitalier Pitié-Salpétrière, Paris, France; INSERM (S.C., M.J.C., A.K.), Dyslipoproteinemia and Atherosclerosis Research Unit 551, Paris France; and the Institute for Translational Medicine and Therapeutics (W.R.L.), University of Pennsylvania, Philadelphia.

Correspondence to Dr W. Sean Davidson, Department of Pathobiology and Laboratory Medicine, University of Cincinnati, Cincinnati OH 45221. E-mail Sean.Davidson{at}UC.edu

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.

Proteomic analyses have revealed that physicochemically-defined particle subpopulations of normolipidemic human HDL are distinguished by distinct protein abundance patterns. Enrichment of apolipoprotein L-I and paraoxonases 1 and 3 in dense HDL3 correlated with the capacity to attenuate LDL oxidation, suggesting that distinct particle-specific protein clusters may profoundly impact HDL function.

Key Words: high density lipoprotein • mass spectrometry • compositional heterogeneity • proteome • oxidation

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