Phospholipid transfer protein mediated conversion of high density lipoproteins generates beta(1)-HDL

High density lipoproteins (HDL) subclasses can be differentiated by two-dimensional non-denaturing polyacrylamide gradient gel electrophoresis (2D-PAGGE) and subsequent immunoblotting. The quantitatively minor HDL-subclasses pre beta(1)-LpA-I and gamma-LpE are initial accepters of cell-derived cholesterol into the plasma compartment. In this study we analysed the effect of phospholipid transfer protein (PLTP) on the electrophoretic distribution of HDL-subclasses in plasma as well as the ability of plasma, pre beta(1)-LpA-I, and gamma-LpE to take up [H-3]cholesterol from labeled fibroblasts. Pre beta(1)-LpA-I but not gamma-LpE disappeared during a 16 hours incubation in the absence of PLTP. During a one minute incubation pre beta(1)-LpA-I of pre-incubated plasma released 75% less [H-3]cholesterol from radiolabeled fibroblasts than pre beta(1)-LpA-I of control plasma. Pre-incubation of plasma reduced the uptake of [H-3]cholesterol by gamma-LpE by 40%. Totally, the cholesterol efflux capacity of plasma decreased by 10% compared to the original sample. The amount of immunodetectable pre beta(1)-LpA-I increased when plasma was incubated in the presence of PLTP while the amount of immunodetectable gamma-LpE did not change. After one minute incubation of PLTP-conditioned plasma with [H-3]cholesterol-labeled fibroblasts, the amount of radioactive cholesterol taken up by pre beta(1)-LpA-I was twice as high as in control plasma whereas the amount of [H-3]cholesterol taken up by gamma-LpE remained unchanged. As a net result, treatment with PLTP increased the cholesterol efflux into total plasma by 40%. Together with results of previous studies our data suggest that the conversion of alpha-LpA-I-3 into alpha-LpA-I-2 by PLTP generates pre beta(1)-LpA-I but not gamma-LpE. PLTP helps to enhance the uptake of cell-derived cholesterol by pre beta(1)-LpA-I and, thereby, the cholesterol efflux capacity of normal plasma.