In vitro modulation of the distribution of normal human plasma high density lipoprotein subfractions through the lecithin: Cholesterol acyltransferase reaction

Abstract

The effect of the lecithin: cholesterol acyltransferase reaction on the chemical composition, morphology and distribution of normal human plasma high density lipoprotein (HDL) subclasses was studied in vitro. Incubation of plasma in the presence of polyenephosphatidylcholine (PPC) resulted in a 45 ± 11% ( n= 6) decrease in unesterified cholesterol after 20 h. This effect was abolished by prior heating of the plasma at 56°C or by the addition of diisopropyl fluorophosphate (DIFP). Plasma triacylglycerol levels were constant. Analysis of the plasma lipoproteins by zonal ultracentrifugation and isopycnic equilibrium banding revealed a bimodal distribution of the HDL of native plasma and both heat-inactivated or DIFP-treated samples with peak maxima at d = 1.084 g/ml and d = 1.110 g/ml. Following the lecithin:cholesterol acyltransferase reaction essentially all of the HDL material had flotation characteristics typical of HDL 2. The peak maximum was d = 1.086 g/ ml. There were no apparent changes in the distribution of the lipoproteins of d < 1.063 g/ml. The newly formed HDL were poor in PC and unesterified cholesterol but rich in cholesteryl ester, sphingomyelin and lyso-PC. The HDL apolipoprotein pattern was unaltered. HDL morphology was not affected by the lecithin: cholesterol acyltransferase reaction. Similar results were obtained in the absence of PPC. However, under these conditions the total phospholipid content of the HDL was reduced and lyso-PC was not demonstrable as a product of the lecithin:cholesterol acyltransferase reaction after 20 h. The results are interpreted to indicate that lecithin:cholesterol acyltransferase is involved in the transformation of HDL 3 into HDL 2.