AMERICAN HEART ASSOCIATION SCIENTIFIC SESSIONS - 98
DALLAS -- Scientists have long known that female sex hormones such as estradiol protect women from cardiovascular disease. But understanding how estradiol protects arteries from the oxidation of low-density lipoprotein (LDL) cholesterol associated with dangerous atherosclerotic plaque formation has eluded researchers.
Emory University researchers offer an explanation at this week's 71st Scientific Sessions of the American Heart Association, suggesting that high levels of estradiol are associated with increased levels of the prooxidant enzyme myeloperoxidase (MPO) -- and that MPO protein oxidizes LDL and clears the oxidized LDL via the liver.
Estradiol may further act as a prooxidant in the oxidation of LDL by MPO. "Based on its ability to inhibit copper-mediated oxidation of LDL, it has been suggested that E2 (estradiol) might act as an antioxidant and prevent the oxidation of LDL," says first author Nalini Santanam, Ph.D., assistant professor of Gynecology and Obstetrics at the Emory University School of Medicine.
To test this concept, the team measured the oxidation of LDL in groups of women with widely varying levels of circulating estradiol: younger and older women, women at different days of the menstrual cycle, and women hyperstimulated with estradiol during in vitro fertilization.
"Our results showed that estradiol at physiologic concentrations had no effect on oxidation, and LDL isolated from these subjects did not differ in its oxidizability in the presence of copper," the team reports.
In contrast, the team noted that LDL isolated from the subjects undergoing in vitro fertilization was readily oxidized by peroxidases -- including MPO. "..our results rule out an antioxidant effect at physiologic concentrations of estradiol," says senior author Sampath Parthasarathy, Ph.D., McCord-Cross Professor and director of research in Gynecology and Obstetrics, and professor of Medicine (Cardiology) at Emory. "We propose a novel hypothesis, that estradiol, by elevating plasma MPO protein levels, may act as a prooxidant and promote the oxidation of LDL. As oxidized LDL is rapidly cleared from plasma by the liver, this would in part account for the beneficial effects of E2 on cardiovascular disease."
The study was supported by the Southeastern Affiliate of the American Heart Association.
(Abstract APS 289.5 -- "The Mechanism by Which Estradiol May Protect Women from Cardiovascular Disease May Involve Myeloperoxidase-mediated Oxidative Clearance of LDL from Plasma." Nov. 11, 1998, 1:30-5 p.m., Dallas Convention Center, Exhibit Hall, Santanam, Nalini; Brewer, Robin; McClatchey, Ruth; Castellano, Penny; Murphy, Ana; Voelkel, Steve; Parthasarathy, Sampath.)
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