ANTIOXIDANT VITAMINS, LIPOPROTEIN OXIDATION & VASOMOTION IN HYPERCHOLESTEROLEMIA

抗氧化维生素、脂蛋白氧化

• 批准号: 3757713
• 负责人: R O CANNON
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3757713
• 关键词: acetylcholine; antioxidants; biological signal transduction; diet therapy; dietary supplements; drug administration rate /duration; human subject; human therapy evaluation; hypercholesterolemia; low density lipoprotein; nitric oxide; nitroferricyanide; nutrition related tag; oxidation; vascular endothelium; vasodilation; vasomotion; vitamin therapy

Animals and humans with hypercholesterolemia have been shown to exhibit impaired endothelium-dependent vasodilation. In vitro studies suggest that oxidatively modified low density lipoprotein (LDL) can impair specific signal transduction pathways that link endothelial cell surface receptor activation to stimulation of nitric oxide production. Recently, antioxidant vitamins have been shown to protect human LDL from oxidative modification. We measured forearm blood flow and oxidative susceptibility of low density lipoproteins in 19 hypercholesterolemic patients and in 14 normal subjects. Vascular responsiveness was determined by infusions of the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator sodium nitroprusside. Oxidative susceptibility of LDL isolated from the plasma of study participants was measured by an in vitro assay. Hypercholesterolemic patients then received daily antioxidant vitamin supplementation (beta carotene 30 mg, vitamin C 1000 mg, vitamin E 800 IU) for one month, with repeat measurement of forearm blood flow responsiveness to the same agonists, and repeat measure of LDL oxidative susceptibility. We found that the maximum forearm flow response to acetylcholine was impaired in patients compared with normal subjects, with similar maximum flow responses to sodium nitroprusside. After one month of antioxidant vitamins the time to onset of LDL oxidation was prolonged by 71plus/minus7% and the maximum rate of oxidation decreased by 26plus/minus25% compared to baseline measurements. However, the maximum forearm blood flow response of hypercholesterolemic patients to acetylcholine on vitamins remained unchanged compared to baseline measurements. Thus, hypercholesterolemic patients have impaired forearm endothelium-dependent vasodilator function. Although one month of antioxidant vitamin supplements to hypercholesterolemic patients reduced the susceptibility of their LDL to oxidation, the impairment in endothelial function remained unaltered. The use of non-vitamin antioxidants or concomitant reduction in LDL levels may be required to show a beneficial effect on endothelial vaso-dilator function and hypercholesterolemic patients.

患有高胆固醇血症的动物和人类表现出 内皮依赖性血管舒张功能受损。 体外研究表明 氧化修饰的低密度脂蛋白（LDL）会损害 连接内皮细胞表面的特异性信号转导途径 受体激活刺激一氧化氮的产生。 最近， 抗氧化维生素已被证明可以保护人体LDL免受氧化损伤， 改性 我们测量了前臂血流量和氧化 19例高胆固醇血症患者低密度脂蛋白易感性研究 正常人14例。 血管反应性为 通过输注内皮依赖性血管扩张剂测定 乙酰胆碱和内皮非依赖性血管舒张剂钠 硝普钠 血浆低密度脂蛋白的氧化敏感性 的研究参与者通过体外测定来测量。 高胆固醇血症患者随后接受每日抗氧化维生素 补充剂（β胡萝卜素30毫克、维生素C 1000毫克、维生素E 800 IU）持续1个月，并重复测量前臂血流量 对相同激动剂的反应性，并重复测量LDL氧化 易感性 我们发现，最大前臂血流反应， 与正常受试者相比，患者的乙酰胆碱受损， 对硝普钠有相似的最大流量反应 经过一 一个月的抗氧化维生素的时间开始LDL氧化是 延长71 ± 7%，最大氧化速率降低 与基线测量值相比增加了26 ± 25%。 但 高胆固醇血症患者前臂最大血流反应 与基线相比，维生素的乙酰胆碱保持不变 测量. 因此，高胆固醇血症患者前臂受损 内皮依赖性血管舒张功能。 虽然一个月的 高胆固醇血症患者的抗氧化维生素补充剂减少 他们的低密度脂蛋白对氧化的敏感性， 内皮功能保持不变。 使用非维生素 可能需要抗氧化剂或伴随的LDL水平降低， 显示出对内皮血管扩张功能有益作用， 高胆固醇血症患者