Abstract
Oxidatively modified low-density lipoprotein may be involved in the adherence of blood monocytes to arterial endothelium in the early atherosclerotic lesion. The present study employed static assays and flow-chamber technique to investigate the adhesive interactions between isolated human blood monocytes and cultured human umbilical vein endothelial cell (EC) monolayer pretreated with Cu 2+-oxidized human plasma LDL (Ox-LDL) and native LDL (N-LDL). The cell-cell binding force was estimated by the intensity of wall shear stress needed to detach monocytes from an EC monolayer. The number of monocytes attached to EC monolayer was quantitated by microscopic observation, measurement of myeloperoxidase (MPO) activity in monocyte and cellular uptake of Rose Bengal stain. The results show that the proadhesive activity of EC surface for monocytes was strongly induced by Ox-LDL and weakly modulated by N-LDL. Pretreatment of an EC monolayer with Ox-LDL (25 μg/ml) for 6 h induced a 2.2-fold increase in the number and an 8-fold increase in the force of monocyte binding to EC monolayer as compared to untreated control. A significant number of monocytes (4.4-times control) were able to maintain their adhesion to Ox-LDL-pretreated EC monolayer under high shear stress (30 dyn/cm 2). The cell surface expression of intercellular adhesion molecule 1 (ICAM-1), but not vascular cell adhesion molecule 1 (VCAM-1), in umbilical vein EC was increased by 2.6-fold after treatment of EC with Ox-LDL (50 μg/ml) for 6 h compared with non-treated control. On prolonged (> 12 h) incubation, Ox-LDL (> 100 μg/ml) was found to have cytotoxic effect on EC as reflected by the loss of EC integrity and detachment at low shear stress. It indicates that a sublethal dose of oxidized LDL may alter vascular endothelium physiology, up-regulate expression of ICAM-1 in EC, enhance monocytes binding against shear-stress-induced detachment, and thus may contribute to atherogenesis.
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Schedule a callMore From: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
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