Proteomic Diversity in HDL: A Driving Force for Particle Function and Target for Therapeutic Intervention

High-density lipoproteins (HDL) are circulating particles composed of phospholipids, cholesterol, and proteins. There is a well established inverse correlation between plasma levels of HDL-associated cholesterol (HDL-C) and the incidence of cardiovascular disease. Attempts at therapeutic interventions to raise plasma HDL-C levels have been successful, raising it by 30% to more than 100%. However, so far, pharmacological raising of HDL-C has provided no benefit in terms of clinical outcomes. In an attempt to understand why, researchers have been looking deeper into the composition and functional properties of HDL. Recent analyses of the protein composition of HDL have discovered that upwards of 70 different plasma proteins are consistently identified on isolated particles. The known functions associated with these proteins are diverse and span physiological roles far beyond the traditional roles for HDL in lipid metabolism, suggesting that novel functional roles for HDL may exist. This information has sparked a new area of research aimed at identifying proteomic subspecies of HDL and understanding their functionality in health and disease. Here we discuss the proteomic diversity of HDL and the concept of subspeciation as well as the influence of disease on HDL-associated proteins and the potential for therapeutic manipulation of the HDL proteome to treat cardiovascular and other inflammatory diseases.