Small, Dense High-Density Lipoprotein-3 Particles Are Enriched in Negatively Charged Phospholipids Relevance to Cellular Cholesterol Efflux, Antioxidative, Antithrombotic, Anti-Inflammatory, and Antiapoptotic Functionalities

TLDR: In this article, the authors characterized the phosphosphingolipidome of major norm-lipidemic HDL subpopulations and related it to HDL functionality, using an original liquid chromatography-mass spectrometry/mass-spectrometry methodology.

Abstract: Objective—High-density lipoprotein (HDL) displays multiple atheroprotective activities and is highly heterogeneous in structure, composition, and function; the molecular determinants of atheroprotective functions of HDL are incompletely understood. Because phospholipids represent a major bioactive lipid component of HDL, we characterized the phosphosphingolipidome of major normolipidemic HDL subpopulations and related it to HDL functionality. Approach and Results—Using an original liquid chromatography–mass spectrometry/mass spectrometry methodology for phospholipid and sphingolipid profiling, 162 individual molecular lipid species were quantified across the 9 lipid subclasses, in the order of decreasing abundance, phosphatidylcholine>sphingomyelin>lysophosphatidylcholine>phosphatidylethanolamine>phosphatidylinositol>ceramide>phosphatidylserine>phosphatidylglycerol>phosphatidic acid. When data were expressed relative to total lipid, the contents of lysophosphatidylcholine and of negatively charged phospha...