Elhage R, Arnal J F, Pieraggi M T, Duverger N, Fiévet C, Faye J C, Bayard F
INSERM U397, Institut L. Bugnard, Toulouse, France.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2679-84. doi: 10.1161/01.atv.17.11.2679.
The reality of the atheroprotective effect of estrogens is still a matter of debate, and its unknown mechanisms could involve favorable changes in blood lipids and lipoproteins and/or direct action at the level of the arterial wall. We used the recently developed animal model of atherosclerosis constituted by apolipoprotein E-deficient mice in an attempt to clarify these issues. Male and female animals, fed a low-fat chow diet, were treated with increasing doses of 17 beta-estradiol (E2) after castration and compared with testosterone treated and uncastrated (intact) animals. Total serum cholesterol, LDL-cholesterol, and HDL-cholesterol concentrations decreased under E2 treatment in each sex and were weakly correlated with lesion area. However, a highly significant correlation between lesion area and serum E2 levels also suggested a direct action of E2 on cells of the vascular wall. A dose-response curve analysis revealed that these activities were sex-dependent, with females being nearly twice as sensitive to E2 as males. It also revealed that the atheroprotective activity was recruited at higher E2 concentrations than those needed by other E2 target tissues such as uterus or functions such as apoA-1 and LDL production and/or clearance rates.
雌激素的抗动脉粥样硬化作用的实际情况仍存在争议，其未知机制可能涉及血脂和脂蛋白的有利变化以及/或者在动脉壁水平的直接作用。我们使用了最近开发的由载脂蛋白E缺乏小鼠构成的动脉粥样硬化动物模型，试图阐明这些问题。将喂食低脂普通饮食的雄性和雌性动物去势后，用递增剂量的17β-雌二醇（E2）进行治疗，并与接受睾酮治疗和未去势（完整）的动物进行比较。在E2治疗下，每种性别的血清总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇浓度均下降，且与病变面积呈弱相关。然而，病变面积与血清E2水平之间高度显著的相关性也表明E2对血管壁细胞有直接作用。剂量-反应曲线分析显示，这些活性具有性别依赖性，雌性对E2的敏感性几乎是雄性的两倍。该分析还表明，与子宫等其他E2靶组织或载脂蛋白A-1和低密度脂蛋白产生及/或清除率等功能所需的浓度相比，在更高的E2浓度下才会产生抗动脉粥样硬化活性。
