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Methods Find Exp Clin Pharmacol. 1997 Apr;19(3):153-9.

Oxidized low density lipoprotein acts on endothelial cells in culture to enhance endothelin secretion and monocyte migration.

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Institute of Clinical Biochemistry, University of Bonn, Germany.


Monocyte deposition on the endothelium is the initial step in atherogenesis. Oxidized low density lipoprotein (Ox-LDL) is involved in the development of the fatty streak which progresses to the atherosclerotic lesion. Our interest focussed on the question, does the endothelium react to Ox-LDL to produce humoral substances that might influence the migration of human blood monocytes? Chemotaxis of monocytes was assessed by the modified membrane-filter technique based on the Boyden chamber principle. Exposure of porcine aorta endothelial cells (ECs) to Ox-LDL (100 micrograms/ml) increased the directional migration of monocytes by 25% (p < 0.01) over that of ECs in the absence of Ox-LDL. Radioimmunoassay of the EC culture media revealed the presence of immunoreactive endothelin-1 (ir-ET-1). The endothelin converting enzyme inhibitor, phosphoramidone (10 microM), when incubated together with ECs and Ox-LDL, suppressed the synthesis of ir-ET-1 by 53% (p < 0.05) and the migration decreased by 12% (p < 0.05). Preincubation of monocytes with the ETA receptor-selective antagonist, BQ-123 (1 microM), followed by exposure to ECs plus Ox-LDL, lead to a decrease in their migration by 12% (p < 0.05) compared to monocytes not treated with BQ-123. These results show that Ox-LDL acts on ECs to enhance the synthesis of ir-ET-1 which in turn increases the directional migration of monocytes. Phosphoramidone decreased the synthesis of ir-ET-1 but migration was affected only modestly; monocyte ETA receptor blockade by BQ-123 also suppressed migration toward EC chemoattractants to a small extent. Both results suggest that in addition to ir-ET-1 other chemotactic factors are being released by the ECs; Ox-LDL appears to enhance their release or synthesis.

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