ESTROGENS AND LIPOPROTEIN OXIDATION

雌激素和脂蛋白氧化

• 批准号: 6184204
• 负责人: CAROLE Lynn BANKA
• 金额: $ 23.46万
• 依托单位: LA JOLLA INST FOR MOLECULAR MEDICINE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6184204
• 关键词: Macaca fascicularis; antiatherogenic agent; antioxidants; atherosclerosis; autoantibody; blood banks; esterification; estradiol; estrogens; female; high density lipoproteins; hormone regulation /control mechanism; human tissue; inflammation; laboratory mouse; low density lipoprotein; oxidation; oxidative stress; peroxidation; phosphatidylcholine sterol acyltransferase

Estrogens are known to protect postmenopausal women from heart disease. An extraordinary range of beneficial effects have been associated with estrogens and the range of mechanisms appear to be equally broad. One overlooked mechanism of estrogen protection is its function as an antioxidant. We have established that estrogen selectively protects high density lipoprotein (LDL) from oxidation in vitro and have preliminary evidence that his mechanism is operational in vivo. The antioxidant protection of HDL is predicted to preserve the antiatherogenic functions of HDL. A mechanism for this selective antioxidant protection of HDL is proposed and will be tested. Furthermore, we hypothesize that estrogen protects from oxidant stress at the cellular level, reducing the inflammatory response to oxidized lipids. To establish the importance of antioxidant actions of strong we propose to 1) confirm that a direct relationship exists between estrone-mediated anti antioxidant protection of HDL seen in vitro is operational in vivo; 3) test the hypothesis that estrogen modulates inflammatory components of atherosclerosis by inhibiting lipid peroxidation and stimulating an autoimmune response. Successful completion of the proposed studies will enhance our understanding of the mechanism of action of estrogens in protecting from heart disease and will contribute useful information for the design of therapeutic selective estrogen receptor modulators (SERMs).

众所周知，雌激素可以保护绝经后妇女免受心脏病的侵害。雌激素具有一系列非凡的有益作用，其作用机制似乎同样广泛。雌激素保护的一个被忽视的机制是其作为抗氧化剂的功能。我们已经确定雌激素在体外选择性地保护高密度脂蛋白（LDL）免于氧化，并有初步证据表明其机制在体内有效。 HDL 的抗氧化保护预计会保留 HDL 的抗动脉粥样硬化功能。提出了一种 HDL 选择性抗氧化保护机制，并将进行测试。此外，我们假设雌激素可以在细胞水平上防止氧化应激，减少对氧化脂质的炎症反应。为了确定强抗氧化作用的重要性，我们建议1）确认体外观察到的雌酮介导的HDL抗氧化保护与体内发挥作用之间存在直接关系； 3）检验雌激素通过抑制脂质过氧化和刺激自身免疫反应来调节动脉粥样硬化炎症成分的假设。成功完成拟议研究将增强我们对雌激素预防心脏病作用机制的理解，并将为治疗性选择性雌激素受体调节剂（SERM）的设计提供有用的信息。