on June 28, 2007
Published online before print June 28, 2007, doi: 10.1161/ATVBAHA.107.142695
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Submitted on September 7, 2006
Accepted on June 7, 2007
Enhanced Levels of Oxidized Low-Density Lipoprotein Prime Monocytes to Cytokine Overproduction via Upregulation of CD14 and Toll-Like Receptor 4 in Unstable Angina
A. Fratta Pasini ;
From the Department of Biomedical and Surgical Sciences, Section of Internal Medicine D (A.F.P., U.G., C.S., M.C.N., V.B., L.C.) and the Section of Cardiology (M.A., E.F., C.V.), University of Verona, Italy.
* To whom correspondence should be addressed. E-mail: luciano.cominacini{at}univr.it.
Objectives--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.
Methods and 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-
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.
Key words: oxidized LDL • IL-6 • IL-1 beta • CD14 • toll-like receptors • monocytes • unstable angina