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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:840-846.)
© 1999 American Heart Association, Inc.

Original Contributions

17ß-Estradiol Reduces Glycoxidative Damage in the Artery Wall

Barbara A. Walsh; Bonnie L. Busch; Adam E. Mullick; Karen M. Reiser; John C. Rutledge

From the Department of Medicine, Division of Cardiovascular Medicine (B.A.W., A.E.M., J.C.R.); the Department of Biological Sciences, Division of Neurobiology, Physiology, and Behavior (B.L.B.); and the Department of Medicine, Division of Pulmonary/Critical Care (K.M.R.), University of California, Davis.

Correspondence to John C. Rutledge, MD, Division of Cardiovascular Medicine, One Shields Ave, University of California, Davis, CA 95616-8636. E-mail jcrutledge{at}ucdavis.edu

Abstract—Glycoxidative damage in the vasculature has been linked to atherosclerotic cardiovascular disease. Estrogens protect against the development and progression of atherosclerosis. Because estrogens are potent antioxidants that also effect glucose metabolism, part of their protection against atherosclerosis could be through attenuation of glycoxidative damage in the vascular wall. In this study, we tested the hypothesis that chronic estradiol administration is associated with decreased levels of glycoxidative damage in arterial walls. We harvested and examined iliac arteries from ovariectomized, 8-month-old rats that had been implanted for 6 months with 1 of the following subcutaneous hormone pellets: low estradiol (2.5 mg estradiol), high estradiol (25 mg estradiol), P₄ (200 mg progesterone), low estradiol and P₄, placebo (no hormone), or control (no implant). Using pentosidine as a biomarker of glycoxidative damage, we found that all vessels from rats receiving estradiol (low estradiol, high estradiol, and low estradiol+P₄) exhibited a 50% reduction in glycoxidative damage compared with P₄, placebo, and control vessels (P<0.05). Consistent with this finding, we observed that estradiol-treated rats had a 30% decrease in tissue levels of hydroperoxides, a marker of oxidative stress. Finally, estradiol-treated rats had a small, but significant, decrease in plasma glucose levels (P<0.01). In summary, we report the novel finding that chronic estrogen administration is associated with significant decreases in glycoxidative damage and oxidative stress in the arterial wall. It seems likely that these actions may constitute a mechanism by which estrogen attenuates the progression of atherosclerosis.

Key Words: estrogen • glycoxidative damage • oxidant stress • glycemic stress • atherosclerosis

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