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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:581.)
© 2002 American Heart Association, Inc.

Vascular Biology

Oxidized Cholesteryl Linoleates Stimulate Endothelial Cells to Bind Monocytes via the Extracellular Signal–Regulated Kinase 1/2 Pathway

Joakim Huber; Herbert Boechzelt; Barbara Karten; Michael Surboeck; Valery N. Bochkov; Bernd R. Binder; Wolfgang Sattler; Norbert Leitinger

From the Department of Vascular Biology and Thrombosis Research (J.H., M.S., V.N.B., B.R.B., N.L.), University of Vienna, Vienna, and the Institute of Organic Chemistry (H.B.), Institute of Biochemistry (B.K.), and Institute of Medical Biochemistry (W.S.), SFB Biomembranes Research Center, University of Graz, Graz, Austria.

Correspondence to Dr Norbert Leitinger, Department of Vascular Biology and Thrombosis Research, University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria. E-mail norbert.leitinger{at}univie.ac.at

Oxidation products of cholesteryl esters have been shown to be present in oxidized low density lipoprotein and in atherosclerotic lesions. Monocyte adhesion to the endothelium is an initiating crucial event in atherogenesis. Here, we show that in vitro oxidized cholesteryl linoleate (oxCL) stimulated human umbilical vein endothelial cells (HUVECs) to bind human peripheral blood mononuclear cells as well as monocyte-like U937 cells but not peripheral blood neutrophils or neutrophil-like HL-60 cells. Among the oxidation products contained in oxCLs, 9-oxononanoyl cholesterol (9-ONC) and cholesteryl linoleate hydroperoxides stimulated U937 cell adhesion. OxCL-induced U937 cell adhesion was inhibited by an antibody against the connecting segment-1 region of fibronectin. Neither oxCL nor 9-ONC induced activation of the classical nuclear factor-B pathway. In contrast, stimulation of HUVECs with oxCL resulted in phosphorylation of the extracellular signal–regulated kinase 1/2. Moreover, U937 cell adhesion induced by 9-ONC and oxCL was blocked by a mitogen-activated protein kinase/extracellular signal–regulated kinase inhibitor and a protein kinase C inhibitor. Taken together, oxCLs stimulate HUVECs to specifically bind monocytes, involving endothelial connecting segment-1 and the activation of a protein kinase C– and mitogen-activated protein kinase–dependent pathway. Thus, oxidized cholesteryl esters may play an important role as novel mediators in the initiation and progression of atherosclerosis.

Key Words: oxidized lipids • cholesteryl linoleate • endothelial cells • monocyte adhesion • atherosclerosis

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