Effects of oxidized low density lipoprotein on endothelin secretion by cultured endothelial cells and macrophages

The aim of this study was to determine how oxidized LDL affects endothelin secretion by endothelial cells, monocytes and macrophages. It was found that different degrees of oxidation of LDL had different effects on endothelin production. Extensively oxidized LDL inhibited endothelin secretion from cultured endothelial cells. It also attenuated endothelin secretion from phorbol ester-activated macrophages. The inhibitory effect on endothelin secretion required a substantial degree of LDL oxidation as reflected by an increase in absorbance at 234 nm (conjugated diene) of 0.7 AU with 125 nM LDL and a two- to three-fold increase in migration distance on electrophoresis. Oxidized LDL inhibited thymidine incorporation in porcine aortic endothelial cells, hence in these cells cytotoxicity may account for at least part of the inhibition of endothelin secretion. Acetyl LDL slightly increased basal endothelin release by endothelial cells, but native LDL or mildly oxidized LDL had no significant effect. Overall, the present findings argue against a stimulatory effect of oxidized LDL on endothelin release as contributing to increased vasoreactivity in atherosclerosis. In fact, the apparent inhibition of endothelin release by extensively oxidized LDL might tend to attenuate vasoreactivity near atherosclerotic lesions.