TY - JOUR
T1 - Physiological concentration of 17β-estradiol retards the progression of severe atherosclerosis induced by a high-cholesterol diet plus balloon catheter injury
T2 - Role of NO
AU - Hayashi, Toshio
AU - Jayachandran, Muthuvel
AU - Sumi, Daigo
AU - Thakur, Navin Kumar
AU - Esaki, Teiji
AU - Muto, Emiko
AU - Kano, Hatsuyo
AU - Asai, Yukako
AU - Iguchi, Akihisa
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2000/6
Y1 - 2000/6
N2 - The molecular mechanisms of the antiatherosclerotic effects of estrogen are not yet known. We evaluated the effects of 17β-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.
AB - The molecular mechanisms of the antiatherosclerotic effects of estrogen are not yet known. We evaluated the effects of 17β-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.
KW - Arteriosclerosis
KW - Balloon injury
KW - Endothelium
KW - Estradiol
KW - Nitric oxide
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U2 - 10.1161/01.ATV.20.6.1613
DO - 10.1161/01.ATV.20.6.1613
M3 - Article
C2 - 10845880
AN - SCOPUS:0033625348
SN - 1079-5642
VL - 20
SP - 1613
EP - 1621
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 6
ER -