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 endoth elin secretion by endothelial cells, monocytes and macrophages. It was found that different degrees of oxidation of LDL had different effect s on endothelin production. Extensively oxidized LDL inhibited endothe lin secretion from cultured endothelial cells. It also attenuated endo thelin secretion from phorbol ester-activated macrophages. The inhibit ory effect on endothelin secretion required a substantial degree of LD L oxidation as reflected by an increase in absorbance at 234 nm (conju gated diene) of 0.7 AU with 125 nM LDL and a two- to three-fold increa se in migration distance on electrophoresis. Oxidized LDL inhibited th ymidine incorporation in porcine aortic endothelial cells, hence in th ese cells cytotoxicity may account for at least part of the inhibition of endothelin secretion. Acetyl LDL slightly increased basal endothel in release by endothelial cells, but native LDL or mildly oxidized LDL had no significant effect. Overall, the present findings argue agains t a stimulatory effect of oxidized LDL on endothelin release as contri buting to increased vasoreactivity in atherosclerosis. In fact, the ap parent inhibition of endothelin release by extensively oxidized LDL mi ght tend to attenuate vasoreactivity near atherosclerotic lesions.