Enhanced plasma levels of oxidized low-density lipoprotein increase circulating nuclear factor-kappa B activation in patients with unstable angina.

Abstract

OBJECTIVES:

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.

BACKGROUND:

Nuclear factor-kB might be involved in atherosclerosis, as is suggested by the presence of activated NF-kB in human atherosclerotic lesions.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Luciano Cominacini, Maurizio Anselmi, Ulisse Garbin, Anna Fratta Pasini, Chiara Stranieri, Massimiliano Fusaro, Cristina Nava, Pierfrancesco Agostoni, Dritan Keta, Pietro Zardini, Tatsuya Sawamura, Vincenzo Lo Cascio
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 46 Issue 5 Pg. 799-806 (Sep 06 2005) ISSN: 0735-1097 [Print] United States
• PMID: 16139128 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol, LDL
• Lipoproteins, LDL
• NF-kappa B
• Receptors, Oxidized LDL
• oxidized low density lipoprotein

Topics

• Aged
• Angina, Unstable (blood, metabolism)
• Case-Control Studies
• Cholesterol, LDL (blood)
• Female
• Humans
• Lipoproteins, LDL (blood)
• Male
• Middle Aged
• NF-kappa B (biosynthesis, blood)
• Receptors, Oxidized LDL (blood)