© 1997 American Heart Association, Inc.
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Antiatherogenic Effect of Estrogen Abolished by Balloon Catheter Injury in Cholesterol-Clamped Rabbits
From the Departments of Obstetrics and Gynecology (P.H.) and Thoracic Surgery (H.õ.A.), Rigshospitalet; the Department of Pathology, Hvidovre Hospital (B.F.H.); and the Department of Clinical Biochemistry, Herlev Hospital (B.G.N.), University of Copenhagen; and the Clinical Institute, University of Odense (S.S.) (Denmark).
Correspondence to Pernille Holm, MD, Department of Women's Healthcare Biology, Novo Nordisk Park, 2760 Måløv, Denmark. E-mail PHlm{at}novo.dk
Abstract The purpose of this study was to investigate the importance of an intact endothelial cell layer on the direct antiatherogenic effect of estrogen on the arterial wall. Thirty rabbits were bilaterally ovariectomized and subjected to mechanical injury of the endothelium by balloon catheterization of the upper thoracic aorta. Immediately after the operation, treatment was initiated with either 17ß-estradiol or placebo given intramuscularly. All rabbits were clamped at a similar plasma cholesterol level from 1 week before the operation until the experiment was terminated 13 weeks later. In the undamaged aorta, ie, the aortic arch, the lower thoracic aorta, and the upper abdominal aorta, the estrogen-treated rabbits had one third (P=.06), one sixth (P=.002), and one seventh (P=.001), respectively, the accumulation of cholesterol of the placebo-treated rabbits. In the upper thoracic aorta that had been subjected to mechanical injury of the endothelium, however, aortic cholesterol accumulation was not significantly different between the two groups. Similar results were obtained by histological evaluation of the aortic tissues. Immunohistochemical staining with antibodies against macrophages, smooth muscle cells, and T lymphocytes revealed no significant differences in the intimal distribution of cells between estrogen- and placebo-treated rabbits, except for a higher number of T lymphocytes per unit intimal area of the undamaged aortic arch (P<.0005) in the estrogen-treated-rabbits than the placebo-treated rabbits. This is the first study to demonstrate that the antiatherogenic effect of estrogen is abolished by balloon catheter injury in cholesterol-clamped rabbits. These results may indicate that an intact endothelial cell layer is crucial for the direct antiatherogenic effect of estrogen on the arterial wall.
Key Words: atherosclerosis • arterial wall • cholesterol • endothelium • 17ß-estradiol
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