Increases in the particle size of high-density lipoproteins induced by purified lecithin: cholesterol acyltransferase: effect of low-density lipoproteins

Abstract

Homogeneous subpopulations of human high-density lipoproteins subfraction-3 (HDL 3) have been incubated at 37°C with purified lecithin : cholesterol acyltransferase, human serum albumin and varying concentrations of human low-density lipoprotiens (LDL). Changes in HDL particle size and composition during these incubations were monitored. Incubation of HDL 3a (particle radius 4.3 nm) in the absence of LDL resulted in an esterification of more than 70% of the HDL free cholesterol after 24 h of incubation. This, however, was sufficient to increase the HDL cholesteryl ester by less than 10% and was not accompanied by any change in particle size. When this mixture was incubated. in the presence of progressively increasing concentrations of LDL, which donated free cholesterol to the HDL, the molar rate of production of cholesteryl ester was much greater; at the highest LDL concentration HDL cholesteryl ester content was almost doubled after 24 h and there was an increase in the HDL particle size up to the HDL 2 range. In the case of HDL3 3b (radius 3.9 nm), there were again only minimal changes in particle size in incubations not containing LDL. In the presence of the highest concentration of LDL tested, however, the particles were again enlarged into the HDL 2 size range after 24 h incubation. These HDL 2-like particles were markedly enriched with cholesteryl ester but depleted of phospholipid and free cholesterol when compared with native HDL 2. Furthermore, the ratio of apolipoprotein A-I to apolipoprotein A-II resembled that in the parent-HDL 3 and was very much lower than that in native HDL 2. It has been concluded that purified lecithin : cholesterol acyltransferase is capable of increasing the size of HDL 3 towards that of HDL 2 but that other factors must operate in vivo to modulate the chemical composition of the enlarged particles.