Thematic Review Series: High Density Lipoprotein Structure, Function, and Metabolism Cardioprotective functions of HDLs

Multiple human population studies have established the concentration of high density lipoprotein (HDL) cholesterol as an independent, inverse predictor of the risk of having a cardiovascular event. Furthermore, HDLs have several well-documented functions with the potential to protect against cardiovascular disease. These include an ability to promote the efflux of cholesterol from macrophages in the artery wall, inhibit the oxidative modification of low density lipoproteins (LDLs), inhibit vascular inflammation, inhibit thrombosis, promote endothelial repair, promote angiogenesis, enhance endothelial function, improve diabetic control, and inhibit hematopoietic stem cell proliferation. There are undoubtedly other beneficial functions of HDLs yet to be identified. The HDL fraction in human plasma is heterogeneous, consisting of several subpopulations of particles of varying size, density, and composition. The functions of the different HDL subpopulations remain largely unknown. Given that therapies that increase the concentration of HDL cholesterol have varying effects on the levels of specific HDL subpopulations, it is of great importance to understand how distribution of different HDL subpopulations contribute to the potentially cardioprotective functions of this lipoprotein fraction. This review summarizes current understanding of the relationship of HDL subpopulations to their cardioprotective properties and highlights the gaps in current knowledge regarding this important aspect of HDL biology.