Thermal Remodeling of Human HDL Particles Reveals Diverse Subspecies

High-density lipoproteins (HDL) are micelle-like particles consisting of a core of triglycerides and cholesteryl esters surrounded by a shell of phospholipid, cholesterol, and apolipoproteins. HDL is considered "good" cholesterol, and its concentration in plasma is used clinically in assessing cardiovascular health. However, these particles vary in structure, composition, and therefore function, and thus can be resolved into subpopulations, some of which have specific cardioprotective properties. Mass measurements of HDL by charge detection mass spectrometry (CD-MS) previously revealed seven distinct subpopulations which could be delineated by mass and charge [Lutomski, C. A. et al. Anal. Chem. 2018]. Here, we investigate the thermal stabilities of these subpopulations; upon heating, the particles within each subpopulation undergo structural rearrangements with distinct transition temperatures. In addition, we find evidence for many new families of structures within each subpopulation; at least 15 subspecies of HDL are resolved. These subspecies vary in size, charge, and thermal stability. While this suggests that these new subspecies have unique molecular compositions, we cannot rule out the possibility that we have found evidence for new structural forms within the known subpopulations. The ability to resolve new subspecies of HDL particles may be important in understanding and delineating the role of unique particles in cardiovascular health and disease.