Proteomic Analysis of Defined HDL Subpopulations Reveals Particle-Specific Protein Clusters
- 1 June 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 29 (6), 870-876
- https://doi.org/10.1161/atvbaha.109.186031
Abstract
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.Keywords
This publication has 48 references indexed in Scilit:
- Control of cholesteryl ester transfer protein activity by sequestration of lipid transfer inhibitor protein in an inactive complexJournal of Lipid Research, 2008
- Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDLJCI Insight, 2007
- Putting cholesterol in its place: apoE and reverse cholesterol transportJCI Insight, 2006
- Comparison of Label-free Methods for Quantifying Human Proteins by Shotgun ProteomicsMolecular & Cellular Proteomics, 2005
- Mass spectrometry‐based analytical tools for the molecular protein characterization of human plasma lipoproteinsProteomics, 2005
- New Insights Into the Regulation of HDL Metabolism and Reverse Cholesterol TransportCirculation Research, 2005
- Lipoproteomics II: Mapping of proteins in high-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometryProteomics, 2005
- Distribution Spectrum of Paraoxonase Activity in HDL FractionsClinical Chemistry, 2004
- Apolipoprotein DBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 2000
- Apolipoprotein J Is Associated with Paraoxonase in Human PlasmaBiochemistry, 1994