ANTIOXIDANT POTENTIAL OF ESTROGENS IN MENOPAUSE

心血管疾病是绝经后妇女死亡的主要原因 在美国，每年约有500,000人死于女性 各州。服用雌激素可减少50% 心血管疾病的发病率和死亡率。目前的证据表明 雌激素的心脏保护作用的大部分是由 通过不涉及循环水平变化的机制 脂蛋白。因为雌激素是假定的抗氧化剂，以及作为过氧化 现在被认为在动脉粥样硬化的形成中起着关键作用 雌激素对女性血浆脂蛋白过氧化的影响 理解雌激素作用机制的潜在重要性 关于心脏病。此外，在绝经后的女性中， 尤其是糖尿病患者，脂蛋白可能处于更高的状态 有利于过氧化。在本提案中，我们将确定： 1.外源性雌激素对绝经后妇女的影响 糖尿病妇女和正常对照妇女对金属/过氧化氢催化血浆的研究 脂蛋白过氧化电位是通过形成 氧化甾醇和脂肪酸氧化产物； 2.服用雌激素的妇女体内低密度脂蛋白的氧化速率 培养中的内皮细胞对氧固醇和丙二醛的影响 编队； 3.雌激素治疗妇女体内分离的低密度脂蛋白对小鼠的影响 用14C油酸测定巨噬细胞的胆固醇酯化反应 注册成立； 4.雌激素对低密度脂蛋白过氧化的抗氧化作用机制 这些研究旨在确定：(A)雌激素(S)是否具有直接的 对内皮细胞形成活性氧的影响 和体外巨噬细胞；或(B)是否保存内源性内容物 抗氧化剂(维生素E、C、β-胡萝卜素)在低密度脂蛋白分子中的含量 在体外氧化过程中；。(C)是否有抗氧化作用。 雌激素(S)与其与低密度脂蛋白分子结合有关；及(D) 雌激素是否会干扰胆固醇的酯化 动脉壁脂质堆积的最重要事件，显示为 由氧化的脂蛋白诱导。 这些研究应该为抗氧化保护提供证据，作为 雌激素降低心血管疾病风险的机制 绝经后妇女的疾病。

Cardiovascular disease is the leading cause of death in postmenopausal women accounting for approximately 500,000 deaths per year in the United States. Estrogen administration results in a 50% reduction in cardiovascular disease morbidity and mortality. Current evidence suggests that the majority of the cardioprotective effect of estrogens is mediated through mechanisms not involving changes in levels of circulating lipoproteins. As estrogens are putative antioxidants, and as peroxidation of lipoproteins is now believed to play a key role in atherogenesis, an effect of estrogens on plasma lipoprotein peroxidation in women is of potential importance in understanding the mechanism of estrogen action with regard to heart disease. Furthermore, in post menopausal women, especially with diabetes, the lipoprotein could be in a state more conducive to peroxidation. In this proposal we will determine: 1. The effect of exogenous estrogen administration to postmenopausal diabetic and normal control women on metal/H2O2 catalyzed plasma lipoprotein peroxidation potential as measured by the formation of oxysterols and fatty acid oxidation products; 2. The rate of oxidation of LDL isolated from women treated with estrogens by endothelial cells in culture in terms of oxysterol and malonaldehyde formation; 3. The effect of LDL isolated from women treated with estrogens on cholesterol esterification by macrophages, as measured by 14C oleic acid incorporation; 4. The mechanism of antioxidant effect of estrogen on LDL peroxidation. These studies are aimed to establish: (a) whether estrogen(s) has direct effect on the formation of reactive oxygen species by endothelial cells and macrophages in vitro; or (b) whether it preserves endogenous content of antioxidants (vitamine E, C, beta-carotene) within the LDL molecule during oxidation in vitro; (c) whether the antioxidant effect of estrogen(s) is related to its incorporation to LDL molecule; and (d) whether estrogen interferes with cholesteryl esterification which is the most important event in lipid accumulation in arterial wall, shown to be induced by oxidized lipoproteins. These studies should provide evidence for antioxidant protection as one of the mechanisms by which estrogens may decrease the risk of cardiovascular disease in postmenopausal women.