Original Contributions |
From the University of Adelaide, Department of Medicine, Royal Adelaide Hospital (D.T.A., M.A.C., P.J.B.), the Cardiovascular Investigation Unit, Royal Adelaide Hospital (K.A.-R.), and the Hanson Centre for Cancer Research, Department of Human Immunology, IMVS (M.A.V., J.R.G.), Adelaide, South Australia, Australia.
Correspondence to Professor Philip J. Barter MBBS, PhD, Department of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, Australia 5000.
AbstractWe have previously
reported that high density lipoproteins (HDLs) inhibit the
cytokine-induced expression of adhesion molecules in
endothelial cells. Here we investigate whether
different preparations of HDLs vary in their ability to inhibit the
expression of vascular cell adhesion molecule-1 (VCAM-1) in human
umbilical vein endothelial cells (HUVECs)
activated by tumor necrosis factor-
(TNF-
). HDLs
collected from a number of different human subjects all inhibited
VCAM-1 expression in a concentration-dependent manner, although the
extent of inhibition varied widely between subjects. The
inhibitory activities of the HDL2 and
HDL3 subfractions isolated from individual subjects also
differed. Whether equated for concentrations of apolipoprotein (apo)
A-I or cholesterol, the inhibitory activity of
HDL3 was superior to that of HDL2. This
difference remained apparent even when the HDL subfractions were
present only during preincubations with the HUVECs and were removed
before activation by TNF-
. To determine whether the
inhibitory effect of HDL3 was influenced by
apolipoprotein composition, preparations of HDL3 were
modified by replacing all of their apo A-I with apo A-II. This change
in apolipoprotein composition had no effect on the ability of the
HDL3 to inhibit endothelial VCAM-1
expression. Thus, it has been shown that different preparations of HDLs
differ markedly in their abilities to inhibit VCAM-1 expression in
cytokine-activated HUVECs. The mechanism underlying the
differences remains to be determined.
Key Words: endothelial cells vascular cell adhesion molecule-1 HDL HDL subfractions atherosclerosis
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