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Arteriosclerosis, Thrombosis, and Vascular Biology
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on October 17, 2002

Arteriosclerosis, Thrombosis, and Vascular Biology. 2002
Published online before print October 17, 2002, doi: 10.1161/01.ATV.0000042202.42136.D0
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Submitted on July 2, 2002
Accepted on October 8, 2002

The Atheroprotective Effect of Dietary Soy Isoflavones in Apolipoprotein E-/- Mice Requires the Presence of Estrogen Receptor-{alpha}

Michael R. Adams *; Deborah L. Golden ; Thomas C. Register ; Mary S. Anthony ; Jeffrey B. Hodgin ; Nobuyo Maeda ; and J. Koudy Williams

From the Department of Pathology/Comparative Medicine (M.R.A., D.L.G., T.C.R., M.S.A., J.K.W.), Wake Forest University Medical Center, Winston-Salem, NC and the Department of Pathology and Laboratory Medicine (J.B.H., N.M.), University of North Carolina, Chapel Hill.

* To whom correspondence should be addressed. E-mail: madams{at}wfubmc.edu.

Objective—Although the mechanisms by which dietary soy inhibits atherosclerosis are unclear, one line of evidence implicates an important role for its phytoestrogenic isoflavones. We sought to determine whether soy isoflavones exert atheroprotective effects through estrogen receptor-dependent processes and, if so, which estrogen receptor subtype (ie, {alpha} or ß) is involved.

Methods and Results—We compared the effects of diets rich in soy protein that were either isoflavone depleted (0.04 mg/g protein isolate) or isoflavone-replete, or Soy(+IF) (1.72 mg/g protein isolate) in apolipoprotein E-deficient (ee) mice that had been crossed with estrogen receptor-{alpha}- and -ß-deficient mice to produce double-knockout {alpha}{alpha}ee and ßßee mice and (estrogen receptor) wild-type controls (AAee and BBee). Both male and ovariectomized female mice were studied (n=10 to 17 per treatment group; total n=201). After 16 weeks, atherosclerosis was assessed by quantifying the aortic content of esterified cholesterol. Atherosclerosis was reduced 20% to 27% (P<0.05) by Soy(+IF) in ßßee, BBee, and AAee mice but was unaffected in {alpha}{alpha}ee mice. The inhibitory effect of Soy(+IF) was unrelated to sex, total plasma cholesterol, VLDL, LDL, and HDL cholesterol.

Conclusions—The results indicate a necessary role for estrogen receptor-{alpha}-dependent processes in mediating the atheroprotective effects of dietary soy isoflavones.
Key words: atherosclerosis • soy • mice • phytoestrogens • estrogen receptors




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