Oxidized phospholipids trigger atherogenic inflammation in murine arteries.
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.


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.
Furnkranz
Alexander
A
Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria.
Schober
Andreas
A
Bochkov
Valery N
VN
Bashtrykov
Pavel
P
Kronke
Gerhard
G
Kadl
Alexandra
A
Binder
Bernd R
BR
Weber
Christian
C
Leitinger
Norbert
N
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D002339:Carotid Arteries / Q000276:immunology / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D054360:Chemokine CXCL1; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000276:immunology; D017874:Immediate-Early Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D036904:Leukocyte Rolling / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010084:Oxidation-Reduction; D019007:P-Selectin / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D013925:Thromboplastin / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014657:Vasculitis / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology
D001057:Apolipoproteins E; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D019007:P-Selectin; D010743:Phospholipids; D014157:Transcription Factors; D013925:Thromboplastin