Differential effects of HDL subpopulations on cellular ABCA1- and SR-BI-mediated cholesterol efflux

Our objective was to evaluate the associations of individual apolipoprotein A- I ( apoA- I)- containing HDL sub-population levels with ABCA1- and scavenger receptor class B type I ( SR- BI)- mediated cellular cholesterol efflux. HDL subpopulations were measured by nondenaturing twodimensional gel electrophoresis from 105 male subjects selected with various levels of apoA- I in pre beta- 1, alpha- 1, and alpha- 3 HDL particles. ApoB- containing lipoprotein- depleted serum was incubated with [ H-3] cholesterol- labeled cells to measure efflux. The difference in efflux between control and ABCA1-upregulated J774 macrophages was taken as a measure of ABCA1- mediated efflux. SR- BI- mediated efflux was determined using cholesterol- labeled Fu5AH hepatoma cells. Fractional efflux values obtained from these two cell systems were correlated with the levels of individual HDL subpopulations. A multivariate analysis showed that two HDL subspecies correlated significantly with ABCA1- mediated efflux: small, lipid- poor pre beta- 1 particles ( P = 0.0022) and intermediate- sized alpha- 2 particles ( P = 0.0477). With regard to SR- BI- mediated efflux, multivariate analysis revealed significant correlations with alpha- 2 ( P = 0.0004), alpha- 1 ( P = 0.0030), pre beta- 1 ( P = 0.0056), and alpha- 3 ( P = 0.0127) HDL particles. These data demonstrate that the small, lipid- poor pre beta- 1 HDL has the strongest association with ABCA1- mediated cholesterol even in the presence of all other HDL subpopulations. Cholesterol efflux via the SR- BI pathway is associated with several HDL subpopulations with different apolipoprotein composition, lipid content, and size.