Enhanced levels of oxidized low-density lipoprotein prime monocytes to cytokine overproduction via upregulation of CD14 and toll-like receptor 4 in unstable angina.
OBJECTIVE
The purpose of this study was to establish whether oxidized low-density lipoprotein (oxLDL) contributes to cytokine overproduction via upregulation of CD14 and toll-like receptor-4 (TLR-4) expression on circulating monocytes of unstable angina (UA) patients.


RESULTS
Expression of CD14 and TLR-4 on circulating monocytes, and the concentration of plasma oxLDL, (interleukin [IL])-6, IL-1 beta, IL-8, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein-1 (MCP-1) were measured in 27 control (C) subjects, 29 patients with stable angina (SA), and 27 with UA. CD14 and TLR-4 expression on monocytes and circulating IL-6, IL-1 beta, and oxLDL were higher in UA than in SA and C subjects (P<0.001). In in vitro experiments, oxLDL increased CD14 and TLR-4 expression (P<0.001) in control monocytes as well as IL-6, IL-1 beta, and at a lower extent TNF-alpha and MCP-1 levels in the supernatant (P from <0.05 to <0.001). The preincubation of sera derived from UA patients but with control monocytes also induced a significant increase of CD14 and TLR-4 expression (P<0.001) and of IL-6 and IL-1 beta production (P<0.001) in the supernatant.


CONCLUSIONS
In UA patients oxLDL may contribute to monocyte overproduction of some cytokines by upregulating CD14 and TLR-4 expression.
Pasini
A Fratta
AF
Department of Biomedical and Surgical Sciences, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
Anselmi
M
M
Garbin
U
U
Franchi
E
E
Stranieri
C
C
Nava
M C
MC
Boccioletti
V
V
Vassanelli
C
C
Cominacini
L
L
D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation
D053583:Interleukin-1beta; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008077:Lipoproteins, LDL; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C099252:oxidized low density lipoprotein