Abstract
Plasma high density lipoproteins (HDL) are small, dense, protein-rich particles compared with other lipoprotein classes; roughly half of total HDL mass is accounted for by lipid components. Phospholipids predominate in the HDL lipidome, accounting for 40-60% of total lipid, with lesser proportions of cholesteryl esters (30-40%), triglycerides (5-12%), and free cholesterol (5-10%). Lipidomic approaches have provided initial insights into the HDL lipidome with identification of over 200 individual molecular lipids species in normolipidemic HDL. Plasma HDL particles, however, reveal high levels of structural, compositional, and functional heterogeneity. Establishing direct relationships between HDL structure, composition, and atheroprotective functions bears the potential to identify clinically relevant HDL subpopulations. Furthermore, development of HDL-based therapies designed to target beneficial subspecies within the circulating HDL pool can be facilitated using this approach. HDL lipidomics can equally contribute to the identification of biomarkers of both normal and deficient HDL functionality, which may prove useful as biomarkers of cardiovascular risk. However, numerous technical issues remain to be addressed in order to make such developments possible. With all technical questions resolved, quantitative analysis of the molecular components of the HDL lipidome will contribute to expand our knowledge of cardiovascular and metabolic diseases.
Highlights
Plasma high density lipoproteins (HDL) are small, dense, protein-rich particles compared with other lipoprotein classes; roughly half of total HDL mass is accounted for by lipid components
Alterations at the level of the HDL lipidome that can impact the antioxidative properties of HDL might involve enrichment in SM and in saturated fatty acids, both resulting in elevated rigidity of the phospholipid surface monolayer of HDL [58]
Modern lipidomic approaches have provided our initial insights into the lipid species profiles of human plasma HDL
Summary
Phospholipids Phospholipids represent the major component of the HDL lipidome, accounting for approximately half of all lipids on a weight basis (Table 1). HDL contains smaller but still significant amounts (у1 wt% of total HDL lipids) of lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and plasmalogens [4, 7, 8] (Table 1). As a result of enrichment in phospholipids, HDL represents a major carrier of PC, LPC, PE, and PE-derived plasmalogens, containing over 50% of each of these lipid classes present in human serum [4]. PC is the key structural phospholipid of cell membranes and lipoproteins, and represents the principal plasma phospholipid that accounts for 33–45 wt% of total lipid in HDL [4] (Table 1).
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