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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1991.)
© 2007 American Heart Association, Inc.

Vascular Biology

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; M. Anselmi; U. Garbin; E. Franchi; C. Stranieri; M.C. Nava; V. Boccioletti; C. Vassanelli; L. Cominacini

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.

Correspondence to L. Cominacini, 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. 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.

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. 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