Effect of the human cholesteryl ester transfer protein on the particle size redistribution of specific subpopulations of high density lipoproteins-3.

ABSTRACT

The effect of the cholesteryl ester transfer protein (CETP) on the size redistribution of high density lipoprotein-3 (HDL3) particles containing either apolipoprotein A-I without apolipoprotein A-II, designated HDL3 (A-I w/o A-II), or apolipoprotein A-I with apolipoprotein A-II, designated HDL3 (A-I w A-II), was investigated by incubating HDL3 at 37 degrees C in the presence of a purified preparation of CETP. At the end of the incubation, the distribution of total HDL3 as well as HDL3 (A-I w/o A-II) particles, recovered after immunoprecipitation of HDL3 (A-I w A-II) particles with anti-apo A-II antibodies, was determined by non-denaturing polyacrylamide gradient gel electrophoresis. Total HDL3 ultracentrifugally isolated from plasma consisted of two distinct subpopulations of particles with apparent diameters of 8.5 and 7.8 nm. The distribution profile of HDL3 (A-I w/o A-II) particles, revealed that the HDL3 subpopulation with a mean diameter of 8.5 nm comprised two typs of particles, containing either only apo A-I or apo A-I with apo A-II, while the lipoprotein subpopulation with a mean diameter of 7.8 nm consisted exclusively of particles containing both apolipoproteins. During incubation at 37 degrees C, CETP induced the redistribution of HDL3 with a mean apparent diameter of 8.5 nm towards particle subpopulations of larger (9.4 nm diameter) and smaller (7.8 and 7.4 nm diameter) size. It was demonstrated that the CETP-mediated conversion of HDL3 concerned both type of particles. CETP preferentially induced the transformation of HDL3 (A-I w A-II) particles with a mean diameter of 8.5 nm into larger (9.4 nm diameter) and smaller (7.8 nm diameter) particles containing apo A-I and apo A-II. Secondly, CETP induced a shift of HDL3 (A-I w/o A-II) particles with a mean diameter of 8.5 nm towards particles of smaller size (7.4 nm diameter) containing only apo A-I, while HDL3 (A-I w A-II) particles with mean diameters of 7.8 and 9.4 nm remained stable. In addition, this study demonstrated that the redistribution of HDL3 particles was accompanied by a dissociation of apolipoprotein A-I from the lipoprotein surfaces. The effect of myristic acid on CETP-induced HDL3 redistribution was mainly due to a redistribution of HDL3 (AI w/o AII) particles.