Effects of bazedoxifene, conjugated equine estrogens, and a tissue-selective estrogen complex containing both bazedoxifene and conjugated equine estrogens on cerebral artery atherosclerosis in postmenopausal monkeys.
Effects of bazedoxifene, conjugated equine estrogens, and a tissue-selective estrogen complex containing both bazedoxifene and conjugated equine estrogens on cerebral artery atherosclerosis in postmenopausal monkeys.
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DOI：
10.1097/gme.0b013e31829370e5
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发表时间：
2014-01
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;Pajewski NM;Golden D;Floyd E;Appt SE
评价新型选择性雌激素受体调节剂醋酸巴多昔芬（bazedoxifene acetate，BZA）和组织特异性雌激素复合物（TSEC = BZA）联合马结合雌激素（conjugated equine estrogens，CEE）对脑动脉粥样硬化程度和严重程度的影响。98只手术绝经后的猴子（Macaca fascicularis）被喂食中度致动脉粥样硬化饮食，然后随机接受不治疗，或女性等效剂量的BZA（20 mg/天），CEE（0.45 mg/天）或BZA+CEE。在20个月的实验期（大约相当于5年的患者经验）后，确定颈总动脉、颈动脉分叉、颈内动脉和基底动脉中的动脉粥样硬化的程度和严重性。使用美国心脏协会分级系统（AHA，0-5级）确定病变严重程度。BZA对脑动脉粥样硬化的程度或严重程度没有一致的不良影响，也没有减弱CEE对颈总动脉粥样硬化严重程度的有益作用。虽然CEE对颈动脉分叉处的动脉粥样硬化程度只有适度的有益影响，但CEE治疗可降低颈总动脉病变的严重程度和受影响病例的数量。如之前报告的，治疗组间的血脂谱无差异。在这项长期（相当于5人患者年）的非人灵长类动物试验中，BZA对脑动脉粥样硬化没有一致的不良影响，也没有减弱CEE对颈总动脉的适度有益作用。此外，CEE抑制颈总动脉复杂斑块的发展
To evaluate the effects of a new selective estrogen receptor modulator (bazedoxifene acetate, BZA) and a tissue specific estrogen complex (TSEC = BZA combined with conjugated equine estrogens (CEE), on atherosclerosis extent and severity of cerebral arteries. 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. After an experimental period of 20 months (approximately equivalent to 5 years of patient experience), the extent and severity of atherosclerosis in the common carotid artery, carotid bifurcation, internal carotid artery and the basilar artery was determined. Lesion severity was determined using the American Heart Association grading system (AHA, grades 0-5). BZA had no consistent adverse effects on the extent or severity of atherosclerosis in the cerebral arteries and did not attenuate the beneficial effects of CEE on common carotid artery atherosclerosis severity. Although CEE had only modest beneficial effects on atherosclerosis extent of the carotid bifurcation, the severity of lesions and numbers of affected cases in the common carotid artery were reduced with CEE treatment. As reported previously, plasma lipid profiles did not differ among the treatment groups. In this long-term (equivalent to 5 human patient years) nonhuman primate trial, BZA had no consistent adverse effect on cerebral artery atherosclerosis and did not attenuate the modest beneficial effect of CEE on common carotid arteries. Furthermore, CEE inhibited the development of complicated plaques in the common carotid artery