Delineation of the Role of Pre-β 1 -HDL in Cholesterol Efflux Using Isolated Pre-β 1 -HDL

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Abstract
Objective— The role of pre-β 1 -high density lipoprotein (pre-β 1 -HDL) in cholesterol efflux was investigated by separating human plasma into purified pre-β 1 -HDL and pre-β 1 -HDL–deficient plasma by using a monoclonal antibody specifically reacting with pre-β 1 -HDL. Methods and Results— When compared with whole plasma, pre-β 1 -HDL–deficient plasma was equally efficient in promoting cholesterol efflux from human skin fibroblasts and THP-1 human macrophage cells. When added at the same apolipoprotein A-I concentration, pre-β 1 -HDL was less effective than whole plasma in promoting cholesterol efflux from fibroblasts but equally effective in promoting cholesterol efflux from THP-1 cells. However, pre-β 1 -HDL–deficient plasma reconstituted with 16% pre-β 1 -HDL was more active than whole plasma, demonstrating that pre-β 1 -HDL does promote cholesterol efflux actively. The amount of cellular cholesterol present in reisolated pre-β 1 -HDL was 1.5- to 2-fold greater after incubation of the cells with whole plasma than after incubation of the cells with pre-β 1 -HDL–deficient plasma or plasma treated with the anti–pre-β 1 -HDL antibody. However, the anti–pre-β 1 -HDL antibody did not inhibit cholesterol efflux. Conclusions— We conclude that whereas pre-β 1 -HDL is capable of taking up cellular cholesterol, its presence in plasma is not essential for cholesterol efflux, at least in vitro. Instead, pre-β 1 -HDL may be the first product of apolipoprotein A-I lipidation during the formation of HDL but may not play a major role in transferring cellular cholesterol to HDL.