OXIDIZED LDL INDUCES TRANSCRIPTION FACTOR ACTIVATOR PROTEIN-1 BUT INHIBITS ACTIVATION OF NUCLEAR FACTOR-KAPPA-B IN HUMAN VASCULAR SMOOTH-MUSCLE CELLS

Oxidized LDL (Ox-LDL) has been implicated in the development of athero sclerotic lesions, mainly due to its enhanced uptake by macrophages an d its ability to alter gene expression in arterial cells. In the prese nt study we demonstrated that Ox-LDL activates activator protein-1 (AP -1), a transcription factor generally induced by mitogenic substances. Lysophosphatidylcholine, which is generated during oxidation of LDL, stimulated AP-1 in a dose-dependent manner. In contrast, the radical-d ependent transcription factor nuclear factor-kappa B (NF-kappa B) was not activated by Ox-LDL, and at a concentration of 50 mu g/mL, Ox-LDL inhibited lipopolysaccharide-induced activation of NF-kappa B. Oxyster ols but not lysophosphatidylcholine inhibited lipopolysaccharide-induc ed NF-kappa B activation, suggesting that they may be responsible for the inhibitory effect of Ox-LDL. In conclusion, Ox-LDL has opposing ef fects on the activities of NF-kappa B and AP-1, suggesting involvement of mechanisms for transcriptional regulation that are strongly affect ed by lipid oxidation products.