STIMULATION OF ENDOTHELIN-1 RELEASE BY LOW-DENSITY AND VERY-LOW-DENSITY LIPOPROTEINS IN CULTURED HUMAN ENDOTHELIAL-CELLS

To examine the effects of lipoproteins on the secretion of endothelin-I from endothelial cells, we measured immunoreactive (ir) endothelin-I release from cultured human umbilical vein endothelial cells in the presence or absence of various concentrations of native low density lipoprotein (LDL), oxidized LDL, and very low density lipoprotein (VLDL). Cultured endothelial cells secreted ir-endothelin-I into serum-free medium in a time-dependent manner, and the secretion was clearly stimulated following a 15-24-h incubation with 10 mug/ml oxidized LDL. The secretion of ir-endothelin-I increased in a dose-dependent manner after a 24-h incubation with oxidized LDL, while only a high dose of native LDL and VLDL significantly increased ir-endothelin-I secretion. The release of ir-endothelin-I stimulated by 20 mug/ml oxidized LDL was reproduced by the same concentration of acetylated LDL but not native LDL. These observations indicate that the release of ir-endothelin-I from endothelial cells is stimulated by lipoproteins, in particular by oxidized LDL, probably through the endothelial scavenger receptor. This increase in ir-endothelin-I release induced by oxidized LDL may contribute to the development of atherosclerotic vascular lesions.