W. Khovidhunkit et al., Cholesterol efflux by acute-phase high density lipoprotein: role of lecithin : cholesterol acyltransferase, J LIPID RES, 42(6), 2001, pp. 967-975
HDL plays an initial role in reverse cholesterol transport by mediating cho
lesterol removal from cells, During; infection and inflammation, several ch
anges in HDL composition occur that may affect the function of HDL; therefo
re, we determined the ability of acute-phase HDL to prc,mote cholesterol re
moval from cells. Acute-phase HDL was isolated from plasma of Syrian hamste
rs injected with lipopolysaccharide. Cholesterol removal from J774 murine m
acrophages by acute-phase HDL was less efficient than that by control HDL b
ecause of both a decrease in cholesterol efflux and an increase in choleste
rol influx, LCAT activity of acute-phase HDL was significantly lower than t
hat of control HDL, When LCAT activity of control HDL was inactivated, chol
esterol efflux decreased and cholesterol influx increased to the level obse
rved in acute-phase HDL, Inactivation of LCAT had little effect on acute-ph
ase HDL, In GM 3468A human fibroblasts, the ability of acute-phase HDL to r
emove cholesterol from cells Tvas also lower than that of normal HDL, The i
mpaired cholesterol removal, however, was primarily a result of an increase
in cholesterol influx without changes in cholesterol efflux, When control
HDL in which LCAT had been inactivated was incubated with fibroblasts, chol
esterol influx increased to a level comparable to th;lt of acute-phase HDL,
without any change in cholesterol efflux. These results suggest that the a
bility of acute-phase HDL to mediate cholesterol removal was impaired compa
red with that of control HDL and the lower LCAT activity in acute-phase HDL
may be responsible for this impairment, The decreased ability of acute-pha
se HDL to remove cholesterol from cells may be one of the mechanisms that a
ccount for the well-known relationship between infection/inflammation and a
therosclerosis. - Khovidhunkit, W., J. K. Shigenaga, A. H. Moser, K. R. Fei
ngold, and C. Grunfeld. Cholesterol efflux by acute-phase high density lipo
protein: role of lecithin:cholesterol acyltransferase.