HDL biology
ApoA-II blocks CETP-driven conversion of reconstituted HDL into small particles, while apoA-I-only HDL splits into both large and small particles (J Lipid Res 1992)
Original title: Changes in the size of reconstituted high density lipoproteins during incubation with cholesteryl ester transfer protein: the role of apolipoproteins
Reconstituted discoidal HDL (r-HDL) particle size distribution is known to change dramatically during in vitro incubation with CETP, and this study tested whether apolipoprotein composition influences these changes. Two r-HDL preparations containing egg phosphatidylcholine and unesterified cholesterol, differing only in apolipoprotein content, were used: one with apoA-I alone (Stokes radius 4.8 nm) and one with apoA-I and apoA-II (radius 4.9 nm). When apoA-I-only r-HDL was incubated with CETP, most 4.8-nm particles converted to smaller (4.3 and 3.9 nm) and larger (8.2 to 13.7 nm) particles. When apoA-I/apoA-II r-HDL was incubated with CETP, larger particles appeared (Stokes radii 8.4 to 11.0 nm) but there was minimal conversion to smaller particles. These results indicate apoA-II inhibits the CETP-driven conversion of r-HDL to small particles.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.