Antioxidant Protection of LDL by Physiological Concentrations of 17ß-Estradiol
Abstract
Background Exposure to estrogens reduces the risk for coronaryartery disease and associated clinical events; however, the mechanismsresponsible for these observations are not clear. Supraphysiologicallevels of estrogens act as antioxidants in vitro, limiting oxidationof low-density lipoprotein (LDL), an event implicated in atherogenesis.We investigated the conditions under which physiological concentrationsof 17ß-estradiol (E2) inhibit oxidative modification ofLDL.Methods and Results Plasma incubated with E2 (0.1 to 100 nmol/L)for 4 hours yielded LDL that demonstrated a dose-related increasein resistance to oxidation by Cu2+ as measured by conjugateddiene formation. This effect was dependent on plasma, becauseincubation of isolated LDL with E2 at these concentrations inbuffered saline produced no effect on Cu2+-mediated oxidation.Incubation of plasma with E2 had no effect on LDL -tocopherolcontent or cholesteryl ester hydroperoxide formation duringthe 4-hour incubation. Plasma incubation with [3H]E2 was associated withdose-dependent association of 3H with LDL. High-performanceliquid chromatographic analysis of LDL derived from plasma incubatedwith [3H]E2 indicated that the majority of the associated specieswere not detectable as authentic E2 but as nonpolar forms ofE2 that were susceptible to base hydrolysis consistent withfatty acid esterification of E2. Plasma-mediated associationof E2 and subsequent antioxidant protection was inhibited by 5,5'-dithio-bis(2-nitrobenzoicacid), an inhibitor of plasma acyltransferase activity.Conclusions Exposure of LDL to physiological levels of E2 ina plasma milieu is associated with enhanced resistance to Cu2+-mediatedoxidation and incorporation of E2 derivatives into LDL. Thisantioxidant capacity may be another means by which E2 limitscoronary artery disease in women.