(Circulation. 1996;94:175-181.)
© 1996 American Heart Association, Inc.
Articles |
Different Effects of Estrogen and Progesterone on Experimental Atherosclerosis inFemale Versus Male Rabbits
Quantification of Cellular Proliferation by Bromodeoxyuridine
the College of Medicine, Department of Internal Medicine, Division of Cardiology (H.H., S.H., V.H.), University of Ulm, and the College of Medicine, Department of Social Medicine--Atherosclerosis Research (G.F., F.W.S.), the Department of Obstetrics and Gynecology (A.O.M.), and the Department of Internal Medicine, Division of Cardiology (A.M.-L., R.H.), University of Tubingen, Germany.
Correspondence to Hartmut Hanke, MD, Department of Internal Medicine, Division of Cardiology, Robert-Koch-Str 8, 89081 Ulm, Germany.
Background The aim of the present study was to compare the effect of estrogen and progesterone on the development of experimental atherosclerosis in female versus male rabbits to assess possible sex-specific differences.
Methods and Results A total of 32 female and 32 male New Zealand White rabbits were ovariectomized or castrated. In addition to a 0.5% cholesterol diet, the rabbits received estradiol alone (1 mg/kg body wt [BW] per week), progesterone alone (25 mg/kg BW per week), or combined estradiol-progesterone in these dosages during 12 weeks. Ovariectomized female and castrated male rabbits served as control groups without hormone treatment. Before excision of the vessels, bromodeoxyuridine labeling was performed to determine the extent of cellular proliferation in the atherosclerotic lesions. The aortic arch was analyzed immunohistologically and morphometrically. An inhibitory effect of estrogen on intimal plaque size was found in female rabbits compared with the ovariectomized control group (0.7±0.5 versus 3.7±2.5 mm2, P<.002; proliferating cells, 3.1±1.8% versus 8.5±2.6%, P<.002). In combination with progesterone, however, estrogen was not able to reduce intimal plaque size or cellular proliferation. In contrast, estradiol in castrated male rabbits was not associated with an inhibitory effect on cellular proliferation or intimal thickening compared with controls (estrogen treatment, 7.6±2.1% proliferating cells and 2.8±1.0 mm2 neointima; control group, 7.2±2.1% cellular proliferation and 2.9±1.2 mm2 intimal thickening).
Conclusions Our data suggest that the atheroprotective effect of estrogen is probably due to a mechanism that is present in female rabbits only.
Key Words: atherosclerosis • hormones • bromodeoxyuridine • muscle, smooth • hypercholesterolemia
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