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on December 9, 2004

Arteriosclerosis, Thrombosis, and Vascular Biology. 2004
Published online before print December 9, 2004, doi: 10.1161/01.ATV.0000153106.03644.a0
A more recent version of this article appeared on March 1, 2005
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Submitted on July 23, 2004
Accepted on November 23, 2004

Oxidized Phospholipids Trigger Atherogenic Inflammation in Murine Arteries

Alexander Furnkranz ; Andreas Schober ; Valery N. Bochkov ; Pavel Bashtrykov ; Gerhard Kronke ; Alexandra Kadl ; Bernd R. Binder ; Christian Weber ; and Norbert Leitinger *

From the Department of Vascular Biology and Thrombosis Research (A.F., V.N.B., G.K., A.K., B.R.B., N.L.), University of Vienna, Austria; Wilheminen Hospital (A.F.), Vienna, Austria; the Department of Cardiovascular Molecular Biology (A.S., C.W.), University of Aachen, Germany; and the Cardiology Research Center (P.B.), Moscow, Russia.

* To whom correspondence should be addressed. E-mail: nl2q{at}virginia.edu.

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-regulated 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.

Conclusion--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.




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