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

Abstract

Abstract —The molecular mechanisms of the antiatherosclerotic effects of estrogen are not yet known. We evaluated the effects of 17β-estradiol (E 2 ) 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 E 2 (100 μg · kg −1 · d −1 ); Group 3, HCD; Group 4, HCD plus a moderate dose of E 2 ; Group 5, HCD plus a low dose of E 2 (20 μg · kg −1 · d −1 ); and Group 6, HCD in nonoophorectomized rabbits. After the treatment phase, plasma E 2 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 E 2 treatment, whereas E 2 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. E 2 restored the impaired abdominal aortic endothelium–dependent relaxation of balloon-injured and HCD-supplemented rabbits, and E 2 increased basal nitric oxide (NO) release. The basal NO–releasing effect showed a significant, inverse relation with the severity of atherosclerosis. Plasma E 2 concentration also showed a significant, inverse relation with atherosclerotic area. In conclusion, physiological concentrations of E 2 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 E 2 .