(Circulation. 1997;95:1378-1385.)
© 1997 American Heart Association, Inc.
Articles |
Antioxidant Protection of LDL by Physiological Concentrations of 17ß-Estradiol
Requirement for Estradiol Modification
From the Evans Memorial Department of Medicine and Whitaker Cardiovascular Institute, Boston (Mass) University Medical Center.
Correspondence to John F. Keaney, Jr, MD, Whitaker Cardiovascular Institute, Room W507, Boston University Medical Center, 80 E Concord St, Boston, MA 02118. E-mail jkeaney{at}acs.bu.edu.
Background Exposure to estrogens reduces the risk for coronary artery disease and associated clinical events; however, the mechanisms responsible for these observations are not clear. Supraphysiological levels of estrogens act as antioxidants in vitro, limiting oxidation of low-density lipoprotein (LDL), an event implicated in atherogenesis. We investigated the conditions under which physiological concentrations of 17ß-estradiol (E2) inhibit oxidative modification of LDL.
Methods and Results Plasma incubated with E2
(0.1 to 100 nmol/L) for 4 hours yielded LDL that demonstrated a
dose-related increase in resistance to oxidation by Cu2+ as
measured by conjugated diene formation. This effect was dependent on
plasma, because incubation of isolated LDL with E2 at these
concentrations in buffered saline produced no effect on
Cu2+-mediated oxidation. Incubation of plasma with
E2 had no effect on LDL 
-tocopherol content or
cholesteryl ester hydroperoxide formation during the 4-hour incubation.
Plasma incubation with [3H]E2 was associated
with dose-dependent association of 3H with LDL.
High-performance liquid chromatographic analysis of LDL derived from
plasma incubated with [3H]E2 indicated that
the majority of the associated species were not detectable as authentic
E2 but as nonpolar forms of E2 that were
susceptible to base hydrolysis consistent with fatty acid
esterification of E2. Plasma-mediated association of
E2 and subsequent antioxidant protection was inhibited by
5,5'-dithio-bis(2-nitrobenzoic acid), an inhibitor of plasma
acyltransferase activity.
Conclusions Exposure of LDL to physiological levels of E2 in a plasma milieu is associated with enhanced resistance to Cu2+-mediated oxidation and incorporation of E2 derivatives into LDL. This antioxidant capacity may be another means by which E2 limits coronary artery disease in women.
Key Words: hormones • lipoproteins • women • antioxidants
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