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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1613.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Physiological Concentration of 17ß-Estradiol Retards the Progression of Severe Atherosclerosis Induced by a High-Cholesterol Diet Plus Balloon Catheter Injury

Role of NO

Toshio Hayashi; Muthuvel Jayachandran; Daigo Sumi; Navin Kumar Thakur; Teiji Esaki; Emiko Muto; Hatsuyo Kano; Yukako Asai; Akihisa Iguchi

From the Department of Geriatrics, Nagoya University School of Medicine, Nagoya, Japan.

Correspondence to Toshio Hayashi, MD, Department of Geriatrics, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466, Japan. E-mail hayashi{at}med.nagoya-u.ac.jp

Abstract—The molecular mechanisms of the antiatherosclerotic effects of estrogen are not yet known. We evaluated the effects of 17ß-estradiol (E₂) on high cholesterol diet– (HCD; standard diet and 1% cholesterol) and balloon injury–induced atherosclerosis in female New Zealand White rabbits. The abdominal aortas of 40 oophorectomized (Groups 1 through 5) and 8 nonoophorectomized (Group 6) rabbits were injured by balloon catheter, and the animals were then divided into the following groups and treated for 10 weeks: Group 1, standard diet; Group 2, standard diet plus a moderate dose of E₂ (100 µg · kg^-1 · d^-1); Group 3, HCD; Group 4, HCD plus a moderate dose of E₂; Group 5, HCD plus a low dose of E₂ (20 µg · kg^-1 · d^-1); and Group 6, HCD in nonoophorectomized rabbits. After the treatment phase, plasma E₂ was increased up to 282.2±45.5 pg/mL in Group 2, 263.0±41.5 pg/mL in Group 4, 87.9±18.8 pg/mL in Group 5, and 45.6±7.3 pg/mL in Group 6. HCD-mediated increases in plasma lipid levels were not changed by E₂ treatment, whereas E₂ decreased the aortic intimal thickening in Group 2 animals compared with those in Group 1 and reduced atherosclerosis in the thoracic and abdominal aortas of Group 4, 5, and 6 rabbits compared with those in Group 3. E₂ restored the impaired abdominal aortic endothelium–dependent relaxation of balloon-injured and HCD-supplemented rabbits, and E₂ increased basal nitric oxide (NO) release. The basal NO–releasing effect showed a significant, inverse relation with the severity of atherosclerosis. Plasma E₂ concentration also showed a significant, inverse relation with atherosclerotic area. In conclusion, physiological concentrations of E₂ can retard the progression of severe atherosclerosis and stabilize atheromas induced by HCD and balloon injury. The retardation may be partially mediated by endothelial NO function in vessels treated with E₂.

Key Words: nitric oxide • estradiol • arteriosclerosis • balloon injury • endothelium

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