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. 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. a procedure performed to view blood vessels after injecting them with a radio-opaque dye that outlines them on X-ray. capacity of HDL to attenuate an inflammatory response induced in arterial wall cells by proinflammatory stimuli. capacity of HDL to protect biomolecules from oxidative damage by one- or two-electron oxidants. capacity of HDL to prevent formation of a thrombus, a stationary blood clot at the wall of a blood vessel. protein that binds and transports lipids in the form of lipoproteins in the circulatory and lymphatic systems; targets lipids to receptors at sites of degradation, storage, transformation and recycling. pathological process that typically underlies cardiovascular morbidity and mortality via formation of atherosclerotic plaques, resulting from the progressive accumulation of cholesterol and diverse lipids in native and oxidised forms, extracellular matrix and inflammatory cells and their debris, in the intima and media of the arterial wall. a non invasively determined parameter, measured by an ultrasound or magnetic resonance imaging, used to assess the thickness of the intima media layers and potentially plaque in the carotid arteries, which are major vessels that supply the brain with blood. capacity of HDL to remove cholesterol from cells. a disorder of lipoprotein metabolism, which involves lipoprotein overproduction, underproduction, overcatabolism and/or undercatabolism. a lipid mediator of inflammation derived from the 20-carbon atom arachidonic acid or a similar fatty acid. The eicosanoids include the prostaglandins, prostacyclin, thromboxane and leukotrienes. a class of cholesterol-rich lipoprotein particles that drive the return of cholesterol from the periphery to the liver; cholesterol carried by these particles is colloquially referred to as ‘good cholesterol’. oxidative degradation of lipids processed by a free radical chain reaction mechanism. plurimolecular, quasi-spherical, pseudomicellar complex composed of lipids solubilised by proteins possessing specialised structure and function, the apolipoproteins. transfer of cholesterol from peripheral cells to the liver for excretion into the bile. lipid-poor, protein-rich discoid and spherical HDL particles of ≤8 nm diameter, with low molecular mass (≤200 kDa) and high density (1.125–1.21 g/ml). a parasitic species that infects the blood, as well as other organs, and causes sickness in livestock and humans. reduction in tension of the blood vessel walls.