PMID- 15591214 OWN - NLM STAT- MEDLINE DCOM- 20051108 LR - 20071115 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 25 IP - 3 DP - 2005 Mar TI - Oxidized phospholipids trigger atherogenic inflammation in murine arteries. PG - 633-8 AB - OBJECTIVE: Lipoprotein-derived phospholipid oxidation products have been implicated as candidate triggers of the inflammatory process in atherosclerosis. However, in vivo evidence regarding the impact of oxidized phospholipids on the artery wall thus far has been elusive. Therefore, the aim of this study was to investigate if structurally defined oxidized phospholipids induce expression of atherogenic chemokines and monocyte adhesion in intact murine arteries. METHODS AND RESULTS: To model the accumulation of oxidized phospholipids in the arterial wall, oxidized 1-palmitoyl-2-arachidonoyl-sn-3-glycero-phosphorylcholine (OxPAPC) was topically applied to carotid arteries in mice using pluronic gel. Using quantitative reverse-transcriptase polymerase chain reaction (PCR) and immunohistochemistry, we show that OxPAPC induced a set of atherosclerosis-related genes, including monocyte chemotactic protein 1 (MCP-1) and keratinocyte-derived chemokine (KC), tissue factor (TF), interleukin 6 (IL-6), heme oxygenase 1 (HO-1), and early growth response 1 (EGR-1). OxPAPC-regulated chemokines were also expressed in atherosclerotic lesions of apolipoprotein E-deficient (ApoE-/-) mice. In isolated perfused carotid arteries, OxPAPC triggered rolling and firm adhesion of monocytes in a P-selectin and KC-dependent manner. CONCLUSIONS: Oxidized phospholipids contribute to vascular inflammation in murine arteries in vivo, initiating atherogenic chemokine expression that leads to monocyte adhesion; therefore, they can be regarded as triggers of the inflammatory process in atherosclerosis. FAU - Furnkranz, Alexander AU - Furnkranz A AD - Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria. FAU - Schober, Andreas AU - Schober A FAU - Bochkov, Valery N AU - Bochkov VN FAU - Bashtrykov, Pavel AU - Bashtrykov P FAU - Kronke, Gerhard AU - Kronke G FAU - Kadl, Alexandra AU - Kadl A FAU - Binder, Bernd R AU - Binder BR FAU - Weber, Christian AU - Weber C FAU - Leitinger, Norbert AU - Leitinger N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20041209 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Apolipoproteins E) RN - 0 (Chemokine CXCL1) RN - 0 (Chemokines) RN - 0 (Chemokines, CXC) RN - 0 (Cxcl1 protein, mouse) RN - 0 (DNA-Binding Proteins) RN - 0 (Early Growth Response Protein 1) RN - 0 (Egr1 protein, mouse) RN - 0 (Immediate-Early Proteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (P-Selectin) RN - 0 (Phospholipids) RN - 0 (Transcription Factors) RN - 9035-58-9 (Thromboplastin) SB - IM MH - Animals MH - Apolipoproteins E/genetics MH - Carotid Arteries/immunology/metabolism MH - Carotid Artery Diseases/*immunology/*metabolism/physiopathology MH - Chemokine CXCL1 MH - Chemokines/metabolism MH - Chemokines, CXC/genetics MH - DNA-Binding Proteins/genetics MH - Early Growth Response Protein 1 MH - Gene Expression/immunology MH - Immediate-Early Proteins/genetics MH - Intercellular Signaling Peptides and Proteins/genetics MH - Leukocyte Rolling/immunology MH - Lipopolysaccharides/pharmacology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Mutant Strains MH - Monocytes/cytology/immunology MH - Oxidation-Reduction MH - P-Selectin/metabolism MH - Phospholipids/*metabolism MH - Thromboplastin/genetics MH - Transcription Factors/genetics MH - Vasculitis/*immunology/*metabolism/physiopathology EDAT- 2004/12/14 09:00 MHDA- 2005/11/09 09:00 CRDT- 2004/12/14 09:00 PHST- 2004/12/14 09:00 [pubmed] PHST- 2005/11/09 09:00 [medline] PHST- 2004/12/14 09:00 [entrez] AID - 01.ATV.0000153106.03644.a0 [pii] AID - 10.1161/01.ATV.0000153106.03644.a0 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2005 Mar;25(3):633-8. doi: 10.1161/01.ATV.0000153106.03644.a0. Epub 2004 Dec 9.