Changes in the size of reconstituted high density lipoproteins during incubation with cholesteryl ester transfer protein: the role of apolipoproteins.

It has been reported previously that the particle size distribution of discoidal, reconstituted HDL (r-HDL) changes dramatically during incubation in vitro with cholesteryl ester transfer protein (CETP). The present study was undertaken in order to determine whether these changes are influenced by the apolipoprotein composition of the r-HDL. Two preparations of r-HDL that contained egg phosphatidylcholine (egg PC) and unesterified cholesterol (UC) but differed in their apolipoprotein composition were used for the study. One preparation contained apolipoprotein (apo) A-I only (A-I w/o A-II r-HDL) while the other contained apoA-I and apoA-II (A-I w A-II r-HDL). The Stokes' radius of the major population of particles in the (A-I w/o A-II) and (A-I w A-II) r-HDL was, respectively, 4.8 and 4.9 nm. When the (A-I w/o A-II) r-HDL were incubated with CETP, most of the particles of radius 4.8 nm were converted to populations of smaller and larger particles. The smaller particles had Stokes' radii of 4.3 and 3.9 nm. The radii of the larger particles ranged from 8.2 to 13.7 nm. When the (A-I w A-II) r-HDL were incubated with CETP larger particles (Stokes' radii = 8.4-11.0 nm) appeared but there was minimal conversion to smaller particles. In addition, a significant proportion of the original (A-I w A-II) r-HDL of radius 4.9 nm was still present at the end of the incubation. These results are consistent with apoA-II inhibiting the conversion of r-HDL to small particles. It is concluded that the apolipoprotein content of r-HDL is an important determinant of the sizes of the particles that are formed during incubation with CETP.