MODULATORS OF OXIDIZED LDL-INDUCED HYPERADHESIVENESS IN HUMAN ENDOTHELIAL-CELLS

The adherence of monocytes to the endothelium is an early event in ath erogenesis. Our previous studies have demonstrated that oxidized LDL i nduced U937 cells-endothelial interactions and that HDL prevented oxid ized LDL effects. Here, we provide evidence that treatment of endothel ial cells with the anti-inflammatory agent indomethacin abolished oxid ized LDL as well as interleukin 1- and lipopolysaccharide-stimulated U 937 adhesion. It is noteworthy that HDL, which is known to be protecti ve against atherosclerosis, was effective only in negating U937 adhesi on induced by oxidized LDL, while it did not affect interleukin 1- and lipopolysaccaride-induced hyperadhesiveness in endothelial cells. Sin ce indomethacin inhibits cyclooxygenase which is the key enzyme in the synthesis of prostanoids, we have studied the effect of oxidized LDL on the expression of cyclooxygenase type 2 and demonstrated that oxidi zed LDL induces a sustained increase in the expression of cylooxygenas e mRNA. (C) 1994 Academic Press, Inc.