Conversion of apolipoprotein-specific high-density lipoprotein populations during incubation of human plasma

Abstract

Incubation studies were performed on plasma obtained from subjects selected for relatively low levels of high-density lipoprotein cholesterol (HDL-C) (no greater than 30 mg/dl) and particle size distributions enriched in the HDL 3 subclass. Incubation (12 h, 37° C) of plasma in the presence or absence of lecithin: cholesterol acyltransferase activity produces marked alteration in size profiles of both major apolipoprotein-specific HDL 3 populations (HDL 3(AI w AII), HDL 3 species containing both apolipoprotein A-I and apolipoprotein A-II, and HDL 3(AI w/o AII), HDL 3 species containing apolipoprotein A-I) as isolated by immunoaffinity chromatography. In the presence or absence of lecithin:cholesterol acyltransferase activity, plasma incubation results in a shift of HDL 3(AI w AII) species (initial mean sizes of major components, approx. 8.8 and 8.0 nm) predominantly to larger particles (mean size, 9.8 nm). A less prominent shift to smaller particles (mean size, 7.8 nm) accompanies the conversion to larger particles only when the enzyme is active. Combined shifts to larger (mean size, 9.8 nm) and smaller (mean size, 7.4 nm) particles are observed for HDL 3(AI w/o AII) particles (mean size, 8.3 nm) also only in the presence of enzyme activity. However, in the absence of enzyme activity, HDL 3(AI w/o AII) species, unlike the HDL 3(AI w AII) species, are converted to smaller (mean size 7.4 nm) rather than to larger particles. Like native HDL 2b(AI w/o AII) particles, the larger HDL 3(AI w/o AII) conversion products exhibit a protein moiety with molecular weight equivalent to four apolipoprotein A-I molecules per particle; small HDL 3(AI w/o AII) products are comprised predominantly of particles with two apolipoprotein A-I per particle. Incubation-induced conversion of HDL 3 particles in the presence of lecithin:cholesterol acyltransferase activity is associated with increased binding of both apolipoprotein-specific HDL populations to low-density lipoproteins (LDL). The present studies indicate that, in the absence of lecithin:cholesterol acyltransferase activity, the two HDL 3 populations follow different conversion pathways, possibly due to apolipoprotein-specific activities of lipid transfer protein or conversion protein in plasma. Our studies also suggest that lecithin:cholesterol acyltransferase activity may play a role in the origins of large HDL 2b(AI w/o AII) species in human plasma by participating in the conversion of HDL 3(AI w/o AII) particles, initially with three apolipoprotein A-I, to larger particles with four apolipoprotein A-I per particle.