Oxidized LDL Induces Transcription Factor Activator Protein–1 but Inhibits Activation of Nuclear Factor–κB in Human Vascular Smooth Muscle Cells

Abstract

Oxidized LDL (Ox-LDL) has been implicated in the development of atherosclerotic lesions, mainly due to its enhanced uptake by macrophages and its ability to alter gene expression in arterial cells. In the present 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-dependent transcription factor nuclear factor-kappa B (NF-kappa B) was not activated by Ox-LDL, and at a concentration of 50 micrograms/mL, Ox-LDL inhibited lipopolysaccharide-induced activation of NF-kappa B. Oxysterols but not lysophosphatidylcholine inhibited lipopolysaccharide-induced NF-kappa B activation, suggesting that they may be responsible for the inhibitory effect of Ox-LDL. In conclusion, Ox-LDL has opposing effects on the activities of NF-kappa B and AP-1, suggesting involvement of mechanisms for transcriptional regulation that are strongly affected by lipid oxidation products.