PMID- 17600225 OWN - NLM STAT- MEDLINE DCOM- 20070906 LR - 20171116 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 27 IP - 9 DP - 2007 Sep TI - Enhanced levels of oxidized low-density lipoprotein prime monocytes to cytokine overproduction via upregulation of CD14 and toll-like receptor 4 in unstable angina. PG - 1991-7 AB - 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-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. FAU - Pasini, A Fratta AU - Pasini AF AD - 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. FAU - Anselmi, M AU - Anselmi M FAU - Garbin, U AU - Garbin U FAU - Franchi, E AU - Franchi E FAU - Stranieri, C AU - Stranieri C FAU - Nava, M C AU - Nava MC FAU - Boccioletti, V AU - Boccioletti V FAU - Vassanelli, C AU - Vassanelli C FAU - Cominacini, L AU - Cominacini L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070628 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Lipoproteins, LDL) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (oxidized low density lipoprotein) SB - IM MH - Aged MH - Angina, Unstable/blood/*metabolism MH - Female MH - Humans MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - Lipopolysaccharide Receptors/*metabolism MH - Lipoproteins, LDL/*physiology MH - Male MH - Middle Aged MH - Monocytes/*metabolism MH - Toll-Like Receptor 4/*metabolism MH - Up-Regulation EDAT- 2007/06/30 09:00 MHDA- 2007/09/07 09:00 CRDT- 2007/06/30 09:00 PHST- 2007/06/30 09:00 [pubmed] PHST- 2007/09/07 09:00 [medline] PHST- 2007/06/30 09:00 [entrez] AID - ATVBAHA.107.142695 [pii] AID - 10.1161/ATVBAHA.107.142695 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2007 Sep;27(9):1991-7. doi: 10.1161/ATVBAHA.107.142695. Epub 2007 Jun 28.