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

作者：William Sean Davidson, R.A. Gangani D. Silva, Sandrine Chantepie, William R. Lagor, M. John Chapman, Anatol Kontush · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2009 · DOI：10.1161/atvbaha.109.186031 · 被引用次数：420 · 研究领域：Paraoxonase enzyme and polymorphisms、Biochemical Acid Research Studies、Blood properties and coagulation

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.