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Journal of Lipid Research, Vol 37, 1704-1711, Copyright © 1996 by Lipid Research, Inc.
N Fournier, M de la Llera Moya, BF Burkey, JB Swaney, J Paterniti Jr, N Moatti, V Atger and GH Rothblat
Sera of transgenic rats expressing human apoA-I were tested for their
ability to stimulate efflux of radiolabeled cholesterol from Fu5AH rat
hepatoma cells. Expression of human apoA-I resulted in a dose-dependent
increase in HDL, as measured by both HDL-cholesterol and HDL- phospholipid,
and produced a decrease in rat apoA-I. In rats expressing high
concentrations of human apoA-I (TgR[hAI]high, human apoA-I > 250 mg/dl),
the increase in HDL-phospholipid was not proportional to the increase in
human apoA-I, as illustrated by a HDL-PL/total apoA-I ratio of 0.84 +/-
0.19 compared to a ratio of 1.28 +/- 0.29 for control rats and of 1.28 +/-
0.39 for rats expressing low levels of human apoA-I (TgR[hAI]low, human
apoA-I < 250 mg/dl). Compared to sera from control animals, efflux of
cell cholesterol was increased by 26% in the sera from TgR[hAI]low, and by
76% in the TgR[hAI]high. An examination of the relationships between efflux
and HDL-related parameters demonstrated a hyperbolic relationship between
efflux and either HDL-cholesterol or HDL-apoA-I. In contrast, there was a
strong linear association (r2 = 0.84) between cholesterol efflux and
HDL-phospholipid, indicating that this parameter is the component of HDL
that best reflects the serum's efflux efficiency. The importance of
phospholipids in modulating cholesterol efflux was further explored by
measuring the effect of supplementation of serum with
dimyristoylphosphatidylcholine (DMPC) vesicles, apoA-I, or both DMPC
vesicles and apoA-I. Whereas addition of human apoA-I had no effect on
efflux, supplementation with DMPC vesicles produced a substantial increase
in efflux that was further stimulated by the combination of DMPC vesicles
and apoA-I. These results demonstrate that a major component of HDL that
modulates cell cholesterol efflux is phospholipid.
ARTICLES
Role of HDL phospholipid in efflux of cell cholesterol to whole serum: studies with human apoA-I transgenic rats
Hospital Broussais Paris, France.
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