Enhanced Plasma Levels of Oxidized Low-Density Lipoprotein Increase Circulating Nuclear Factor-Kappa B Activation in Patients With Unstable Angina

Abstract

The purpose of this study was to investigate the effect of circulating levels of oxidized low-density lipoprotein (ox-LDL) on nuclear factor-kappa B (NF-kB) activation in peripheral blood mononuclear cells (PBMC) of patients with unstable angina (UA) or stable angina (SA) and control subjects. Nuclear factor-kB might be involved in atherosclerosis, as is suggested by the presence of activated NF-kB in human atherosclerotic lesions. Levels of plasma ox-LDL and circulating NF-kB in PBMC (and in separated lymphocytes and monocytes) were measured in 27 control subjects and 29 SA and 27 UA patients. In in vitro studies, the effect of ox-LDL and of the sera derived from a subgroup of UA patients and control subjects on monocytic NF-kB activation was also evaluated. The UA and SA patients had higher levels of circulating ox-LDL and NF-kB in PBMC than control subjects (p < 0.001). The increase in circulating NF-kB was mainly due to the activation of monocytes. In the in vitro studies, ox-LDL dose-dependently increased the activation of NF-kB in monocytes, but not in lymphocytes derived from healthy volunteers. This increase was related to the expression of lectin-like ox-LDL receptor-1 on monocytes. The incubation of monocytes with the sera derived from the UA patients induced a significant increase in NF-kB activation compared with the sera derived from the control subjects. The data suggest that the activation of NF-kB in monocytes of UA patients is, at least in part, induced by circulating molecules such as ox-LDL, which has been found to be particularly elevated in UA patients.