Biological Activities of HDL Subpopulations and Their Relevance to Cardiovascular Disease

The concept of raising high-density lipoprotein (HDL) has been the focus of increasing attention as a strategy to reduce cardiovascular disease. HDL particles are, however, highly heterogeneous in structure, intravascular metabolism and biological activity. In this review, we describe major HDL subpopulations and discuss new findings on the antiatherogenic properties of HDL particles. Across the HDL subpopulation spectrum, small, dense, protein-rich HDLs display potent atheroprotective properties, which can be attributed to specific clusters of proteins and lipids; such activities can be compromised under conditions of atherogenic dyslipidemia. Comprehensive structural and compositional analyses of HDL may provide key information to identify subpopulations displaying specific biological functions and acquiring deficient functionality, with the potential to reveal novel biomarkers of cardiovascular risk and new pharmacological targets.