Proteomic diversity of high density lipoproteins: our emerging understanding of its importance in lipid transport and beyond

Recent applications of mass spectrometry technology have dramatically increased our understanding of the proteomic diversity of high density lipoproteins (HDL). Depending on the method of HDL isolation, upwards of 85 proteins have been identified, and the list continues to grow. In addition to proteins consistent with traditionally accepted roles in lipid transport, HDL carries surprising constituents, such as members of the complement pathway, protease inhibitors involved in hemostasis, acute-phase response proteins, immune function mediators, and even metal-binding proteins. This compositional diversity fits well with hundreds of studies demonstrating a wide functional pleiotrophy, including roles in lipid transport, oxidation, inflammation, hemostasis, and immunity. This review summarizes the progression of our understanding of HDL proteomic complexity and points out key experimental observations that reinforce the functional diversity of HDL. The possibility of specific HDL subspecies with distinct functions, the evidence supporting this concept, and some of the best examples of experimentally defined HDL subspecies are also discussed. Finally, key challenges facing the field are highlighted, particularly the need to identify and define the function of HDL subspecies to better inform attempts to pharmacologically manipulate HDL for the benefit of cardiovascular disease and possibly other maladies.