Effects of bazedoxifene alone and with conjugated equine estrogens on coronary and peripheral artery atherosclerosis in postmenopausal monkeys.
Effects of bazedoxifene alone and with conjugated equine estrogens on coronary and peripheral artery atherosclerosis in postmenopausal monkeys.
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DOI：
10.1097/gme.0b013e318271e59b
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发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
Appt SE
中科院分区：
文献类型：
--
作者：
Clarkson TB;Ethun KF;Chen H;Golden D;Floyd E;Appt SE
目的：观察新型选择性雌激素受体调节剂醋酸巴泽昔芬(BZA)对猴冠状动脉和外周动脉粥样硬化的影响，并观察其是否拮抗结合马类雌激素(CEE)的动脉粥样硬化保护作用。98只接受手术治疗的绝经后猕猴(Macaca Fascularis)被喂以中等致动脉粥样硬化的饮食，然后被随机分成不接受任何治疗的组，或者接受等量的BZA(每天20毫克)、CEE(0.45 mg/天)或BZA+CEE的治疗。试验期为20个月(约相当于5年的患者经验)，在此期间对心血管危险因素采取临时措施。在实验结束时，量化冠状动脉和髂动脉粥样硬化的程度和严重程度。体重、肥胖、空腹血糖浓度和血脂谱在不同的治疗条件下没有差异。与未治疗组相比，BZA对冠状动脉和髂总动脉的动脉粥样硬化程度或严重程度均无不良影响。在诱导绝经后不久给予CEE，对髂动脉和冠状动脉的范围和严重程度都有很强的动脉保护作用。在CEE处理中加入BZA可拮抗CEE的动脉粥样硬化保护作用。在这项非人类灵长类动物试验中，单独使用BZA、单独使用CEE以及BZA和CEE联合使用对血脂谱没有显著影响。CEE明显抑制冠状动脉和髂动脉粥样硬化的进展和并发症。BZA对动脉粥样硬化无不良影响，但可减弱CEE的动脉保护作用。
The objective was to evaluate the effects of bazedoxifene acetate (BZA), a new selective estrogen receptor modulator, on coronary and peripheral artery atherosclerosis and to determine if it would antagonize the atheroprotective effects of conjugated equine estrogens (CEE) in a monkey model. Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and then randomized to receive no treatment, or women’s equivalent doses of BZA (20 mg/day), CEE (0.45 mg/day) or BZA+CEE. The experiment period was for 20 months (approximately equivalent to 5 years of patient experience) during which interim measures were made of cardiovascular risk factors. At the end of the experimental period, the extent and severity of coronary and iliac artery atherosclerosis was quantified. Body weight, adiposity, fasting glucose concentrations and plasma lipid profiles were not different among treatment conditions. BZA had no adverse effects on coronary artery nor common iliac artery atherosclerosis extent or severity when compared to no-treatment. CEE, administered soon after inducing menopause, had a robust atheroprotective effect on both iliac and coronary artery extent and severity. The addition of BZA to the CEE treatment antagonized the atheroprotective effect of the CEE. In this nonhuman primate trial, treatment with BZA alone, CEE alone and BZA and CEE in combination did not have significant effects on plasma lipid profiles. CEE markedly inhibited the progression and complication of both coronary and iliac artery atherosclerosis. BZA had no adverse effects on atherosclerosis but attenuated the atheroprotective effects of CEE.