Oxidized high-density lipoproteins modulate endothelin secretion by adult XXXX aortic endothelial cells.

@entity19858 @entity731 @entity291 @entity165
BACKGROUND: High-density lipoprotein (HDL) @entity165 levels are well established as an inverse risk factor for @entity731 . This fact is probably related to the ability of HDL to induce @entity165 efflux from the vascular cell. It is also possible that HDL affects the production of different mediators implicated in the development of atheroslerosis. Endothelin is a vasconstricting mitogenic peptide involved in the development of @entity731 . We studied whether native HDL, oxidized HDL and @entity19858 HDL modulate the endothelin secretion of cultured adult @entity291 aortic endothelial cells. METHODS: We determined the effect of native HDL and modified HDLs (oxidized HDL and @entity19858 HDL) on the secretion of endothelin by cultured adult @entity291 aortic endothelial cells. An endothelin radioimmunoassay system was used to quantify levels of immunoreactive endothelin in the cultured media. RESULTS: Native HDL, @entity19858 HDL and oxidized HDL produced a highly significant stimulation of endothelin secretion (maximum 294% of control), even at low concentrations (10 and 20 micrograms/ml). Oxidized HDL2 and oxidized HDL3 produced a biphasic effect, with maximum secretion occurring with 100 micrograms/ml oxidized HDL3 (294% of control) and 50 micrograms/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 @entity19858 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 @entity19858 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.
