ABCA1-Mediated Structural Diversity of HDL Subspecies and Their Proposed Roles in Cardioprotection

The compositional and structural heterogeneity of plasma HDL (high-density lipoprotein) underlies its multiple proposed cardioprotective functions. This review explores current ideas for how the structural diversity of HDL particles arises during their biogenesis through ABCA1 (ATP-binding cassette transporter A1)-mediated efflux of membrane phospholipids and cholesterol to APOA1 (apolipoprotein A1), HDL's major protein. The proposed mechanisms driving the formation of nascent HDL particles, varying in size and in the number of APOA1 and lipid molecules they contain, are described. Subsequent remodeling in the plasma compartment produces HDL subspecies with distinct sets of associated proteins. The role of differently sized HDL particles in promoting reverse cholesterol transport by the ABCA1 pathway is relatively well understood. However, additional research is needed to confirm the clinical significance of this pathway. It is also important to determine how, and whether, the antioxidative, immunologic, and anti-inflammatory properties of HDL subspecies, including those containing low-abundance proteins, contribute to cardioprotection.