INHIBITION OF VASCULAR CELL ADHESION MOLECULE EXPRESSION BY HIGH DENSITY LIPOPROTEINS.
D.T. Ashby*, K.-A. Rye, J.R. Gamble, M.A. Vadas and P.J. Barter.
Cardiovascular Investigation Unit, Royal Adelaide Hospital, Adelaide.
High density lipoproteins (HDLs) have been shown `in vitro'to inhibit the expression of adhesion molecules on endothelial cells. These studies investigate the effects of HDL subpopulations, HDL composition and acute-phase HDLs on vascular cell adhesion molecule- 1 (VCAM-1) expression in endothelial cells.
The HDLs were isolated from human plasma by sequential ultracentrifugation. HDL apolipoprotein composition was modified by displacing apoA-I with apoA-II or serum amyloid-A (SAA). The various HDL populations isolated were added at increasing concentrations to cultures of human umbilical vein endothelial cells (HUVECs). The cells were then stimulated with tumour necrosis factor- a and VCAM- 1 expression was determined by flow cytometry.
All types of HDLs tested inhibited VCAM-1 expression in a concentration dependent manner. HDL3 was a superior inhibitor of VCAM-1 expression than HDL, when added to the cells according to apoA-1 or total cholesterol concentration. Acute phase HDL3 containing SAA were as effective as unmodified HDL3 in the inhibition of VCAM- 1 expression. Altering the apolipoprotein composition of the HDLs by displacing the apoA-I with either apoA-II or SAA made no difference to the inhibitory ability of the HDLS. HDLs were broken down into their lipid and protein components and neither of these alone had any inhibitory effect on VCAM-1 expression in the HUVECs. Reconstituted HDLs containing only apolipoproteins and phospholipids had the ability to inhibit VCAM-1 expression in the HUVECS.
In conclusion, the ability of HDLs to inhibit endothelial VCAM-1 expression is independent of their apolipoprotein composition and the HDLs need both apolipoproteins and phospholipids to be present.
