Enhanced plasma levels of oxidized low-density lipoprotein increase circulating nuclear factor-kappa B activation in patients with unstable angina.
OBJECTIVE
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.
Cominacini
Luciano
L
Department of Biomedical and Surgical Sciences, Section of Internal Medicine, University of Verona, Verona, Italy. luciano.cominacini@univr.it
Anselmi
Maurizio
M
Garbin
Ulisse
U
Fratta Pasini
Anna
A
Stranieri
Chiara
C
Fusaro
Massimiliano
M
Nava
Cristina
C
Agostoni
Pierfrancesco
P
Keta
Dritan
D
Zardini
Pietro
P
Sawamura
Tatsuya
T
Lo Cascio
Vincenzo
V
D000368:Aged; D000789:Angina, Unstable / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000096:biosynthesis* / Q000097:blood; D051131:Receptors, Oxidized LDL / Q000097:blood
D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D051131:Receptors, Oxidized LDL; C099252:oxidized low density lipoprotein