Hayek T, Oiknine J, Brook JG, Aviram M:
Role of HDL apolipoprotein E in cellular cholesterol efflux: studies
in apo E knockout transgenic mice.
Biochemical & Biophysical Research Communications 1994 Dec
15;205(2):1072-8
ABSTRACT
The role of apo E in aspects of reverse cholesterol transport was
studied in apolipoprotein E-deficient mice. These animals develop
rampant atherosclerosis. The efflux of cholesterol from mouse
peritoneal macrophages (MPM) was 40% lower when induced by high
density lipoprotein (HDL) from apo E-deficient mice, compared to the
effect of HDL from normal mice. On adding apo E to apo E-deficient
HDL, cholesterol efflux from the macrophages increased by 35%,
approaching the degree of efflux obtained with normal HDL. This HDL
(normal or apo E-deficient)-induced cholesterol efflux was similar
in peritoneal macrophages derived from both normal and apo
E-deficient mice, suggesting that the HDL apo E rather than the
macrophage apo E is responsible for the stimulation of cellular
cholesterol efflux. On determining cholesterol efflux specifically
from the macrophage plasma membrane, the level of efflux was similar
for both HDL preparations, suggesting that apo E in HDL is important
for cholesterol translocation to the plasma membrane, the initial
step in reverse cholesterol transport. It is concluded that the
enhanced atherosclerosis in apo E-deficient mice could be related,
at least partly, to the impaired efflux of LDL derived cholesterol
from macrophages of the arterial wall.
