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 17β-estradiol (E₂) could be incorporated into LDL and high-density lipoprotein (HDL) particles inhibiting lipoprotein oxidation. Introduction of small amounts of esterified E₂ into lipoproteins by means of incubation of free E₂ and E₂ 17-stearate in plasma did not result in any antioxidant effect. Using an artificial transfer system (Celite dispersion), larger amounts of E₂ esters could be incorporated into lipoproteins. Concentrations ranging between 0.27 and 1.38 molecules/LDL particle for E₂ 17-stearate and between 0.36 and 1.93 molecules/LDL particle for E₂ 17-oleate resulted in increased Cu²⁺-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 E₂ esters using Celite as transfer system. Our results suggest that free E₂ can be esterified and incorporated into lipoproteins during incubation in plasma. However, incorporation of supraphysiologic concentrations of E₂ esters into lipoproteins by means of the artificial transfer system was required in order to reduce their oxidation susceptibility. Copyright (C) 1999 Elsevier Science B.V.