Antioxidant protection of lipoproteins containing estrogens: in vitro evidence for low- and high-density lipoproteins as estrogen carriers.

Some recent studies have reported that low-density lipoprotein (LDL) isolated from estrogen-treated postmenopausal women exhibited increased oxidation resistance ex vivo. However, the underlying mechanisms responsible for this effect are not clear. We explored the possibility that lipophilic derivatives of 17beta-estradiol (E(2)) could be incorporated into LDL and high-density lipoprotein (HDL) particles inhibiting lipoprotein oxidation. Introduction of small amounts of esterified E(2) into lipoproteins by means of incubation of free E(2) and E(2) 17-stearate in plasma did not result in any antioxidant effect. Using an artificial transfer system (Celite dispersion), larger amounts of E(2) esters could be incorporated into lipoproteins. Concentrations ranging between 0.27 and 1.38 molecules/LDL particle for E(2) 17-stearate and between 0.36 and 1.93 molecules/LDL particle for E(2) 17-oleate resulted in increased Cu(2+)-induced oxidation resistance of LDL as indicated by statistically significant lag time prolongations. Significant prolongations of lag times were also observed for HDL following incorporation of E(2) esters using Celite as transfer system. Our results suggest that free E(2) can be esterified and incorporated into lipoproteins during incubation in plasma. However, incorporation of supraphysiologic concentrations of E(2) esters into lipoproteins by means of the artificial transfer system was required in order to reduce their oxidation susceptibility.