FACTORS INFLUENCING THE ABILITY OF HDL TO INHIBIT EXPRESSION OF VASCULAR CELL-ADHESION MOLECULE-1 IN ENDOTHELIAL-CELLS

We have previously reported that high density lipoproteins (HDLs) inhi bit the cytokine-induced expression of adhesion molecules in endotheli al cells. Here we investigate whether different preparations of HDLs v ary in their ability to inhibit the expression of vascular cell adhesi on molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVE Cs) activated by tumor necrosis factor-alpha (TNF-alpha). HDLs collect ed from a number of different human subjects all inhibited VCAM-1 expr ession in a concentration-dependent manner, although the extent of inh ibition varied widely between subjects. The inhibitory activities of t he HDL2 and HDL3 subfractions isolated from individual subjects also d iffered. Whether equated for concentrations of apolipoprotein (apo) A- I or cholesterol, the inhibitory activity of HDL, was superior to that of HDL2. This difference remained apparent even when the HDL subfract ions were present only during preincubations with the HUVECs and were removed before activation by TNF-alpha. To determine whether the inhib itory effect of HDL, was influenced by apolipoprotein composition, pre parations 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 HDL, to inhibit endothelial VCAM-1 expression. Thus , it has been shown that different preparations of HDLs differ markedl y in their abilities to inhibit VCAM-1 expression in cytokine-activate d HUVECs. The mechanism underlying the differences remains to be deter mined.