Oxidized High-Density Lipoproteins Modulate Endothelin Secretion by Adult Bovine Aortic Endothelial Cells

Abstract

Background: High-density lipoprotein (HDL) cholesterol levels are well established as an inverse risk factor for atherosclerosis. This fact is probably related to the ability of HDL to induce cholesterol efflux from the vascular cell. It is also possible that HDL affects the production of different mediators implicated in the development of atherosclerosis. Endothelin is a vasoconstricting mitogenic peptide involved in the development of atherosclerosis. We studied whether native HDL, oxidized HDL and tetranitromethane HDL modulate the endothelin secretion of cultured adult bovine aortic endothelial cells.

Methods: We determined the effect of native HDL and modified HDLs (oxidized HDL and tetranitromethane HDL) on the secretion of endothelin by cultured adult bovine aortic endothelial cells. An endothelin radioimmunoassay system was used to quantify levels of immunoreactive endothelin in the cultured media.

Results: Native HDL, tetranitromethane HDL and oxidized HDL produced a highly significant stimulation of endothelin secretion (maximum 294% of control), even at low concentrations (10 and 20 μg/ml). Oxidized HDL₂ and oxidized HDL₃ produced a biphasic effect, with maximum secretion occurring with 100 μg/ml oxidized HDL₃ (294% of control) and 50 μg/ml oxidized HDL₂ (252% of control). The secretion of the peptide decreased with higher concentrations of oxidized HDL₂ and oxidized HDL₃.

Conclusion: Because modified HDLs (oxidized HDL and tetranitromethane HDL) do not bind to the ‘HDL receptor’ to stimulate endothelin secretion, we propose that the stimulation of secretion is mediated by unspecific binding of the lipoprotein to the cell membrane. Nevertheless, oxidized HDL and tetranitromethane HDL may stimulate endothelin secretion via the scavenger-receptor pathway. Our results suggest that HDL and modified HDL participate in the regulation of vascular tone.