Modifying Oxidative Damage in WAVE

修改 WAVE 中的氧化损伤

• 批准号: 6406095
• 负责人: MICHAEL W. STEFFES
• 金额: $ 25.5万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6406095
• 关键词: DNA damage; acute phase protein; angiography; ascorbate; atherosclerotic plaque; biomarker; clinical research; estrogens; female; hormone therapy; human data; human middle age (35-64); human old age (65+); human subject; human therapy evaluation; lipid metabolism; oxidation reduction reaction; oxidative stress; oxidized lipid; protein metabolism; tocopherols; vitamin therapy; women's health; DNA damage; acute phase protein; angiography; ascorbate; atherosclerotic plaque; biomarker; clinical research; estrogens; female; hormone therapy; human data; human middle age (35-64); human old age (65+); human subject; human therapy evaluation; lipid metabolism; oxidation reduction reaction; oxidative stress; oxidized lipid; protein metabolism; tocopherols; vitamin therapy; women's health

Supplemental vitamin E has been associated with a reduced risk of recurrent myocardial infarctions, with efficacy related to dosage and the duration of treatment. Its effects may be enhanced by vitamin C, an antioxidant that can regenerate vitamin E activity. Theoretically vitamin E and C (VitE/C) accumulate in the vascular wall with a concurrent reduction in oxidative damage, a primary feature of atherosclerotic lesions. Estrogen/hormone replacement therapy (HRT) also may reduce oxidative damage, and it may enhance the effect of vitamin E and C. These hypotheses are supported by studies defining oxidation-dependent accumulation of lipids in developing atherosclerosis; the detection of oxidative damage products, such as oxidized-LDL particles, in human atherosclerotic lesions; and clinical studies associating antioxidant or estrogen supplementation with reductions in oxidative damage cardiovascular disease. Nevertheless, no human studies have evaluated the effect of long-term VitE/C treatment, which has been reported as being the most effective prevention factor by epidemiologic studies, on specific. biochemical markers of oxidative damage and concurrently their association with recurrent cardiovascular disease. In addition, no studies have characterized the effect of long-term HRT on markers of oxidative damage or HRT's potential synergistic effect with VitE/C therapy. We propose assaying specific biochemical measures of oxidative damage (all markers at closeout and nitrotyrosine and chlorotyrosine also at baseline) in the Women's Angiographic Vitamin and Estrogen (WAVE) Trial, which randomized 420 38-86 year old women with a prior cardiovascular disease event to placebo, VitE/C, HRT or the combination of VitE/C and HRT. WAVE will determine the efficacy of these treatments on quantitative angiographic evaluation of minimal coronary artery diameter performed at baseline and at the final visit to be completed during the first 10 months of 2001. We will measure oxidation products from several classes of compounds (lipids by F2-isoprostanes, proteins by nitrotyrosine and chlorotyrosine, and DNA by 8-hydroxy-2'-deoxyguanosine), thereby studying several major pathways that may lead to atherogenesis. In addition, inflammation with C-reactive protein, platelet activation with p-selectin, altered lipid metabolism with a lipid profile and other characteristics of the study population will be integrated into the assessment of oxidative damage in WAVE. By measuring these various factors and by assessing oxidative damage in several classes of compounds, we can test the relationships among specific pathways of oxidative damage, supplemental VitE/C and/or HRT and other risk factors upon the progression of established macrovascular disease.

补充维生素E与复发性心肌梗死的风险降低有关，并具有与剂量和治疗持续时间有关的功效。维生素C可能会增强其作用，维生素C是一种可以再生维生素E活性的抗氧化剂。理论上维生素E和C（VITE/C）积聚在血管壁中，并同时减少氧化损伤，这是动脉粥样硬化病变的主要特征。雌激素/激素替代疗法（HRT）也可能减少氧化损伤，并可能增强维生素E和C的作用。这些假设得到了定义脂质中脂质的氧化依赖性积累的研究支持。在人动脉粥样硬化病变中检测氧化损伤产物，例如氧化-LDL颗粒；以及将抗氧化剂或雌激素补充剂与氧化损伤心血管疾病减少相关的临床研究。然而，没有人类研究评估了长期VITE/C治疗的影响，据报道，这是流行病学研究对特异性研究的最有效预防因素。氧化损伤的生化标志物以及它们与复发性心血管疾病的关联。此外，尚无研究表征长期HRT对氧化损伤标记或HRT对VITE/C治疗的潜在协​​同作用的影响。我们在女性血管造影维生素和雌激素（WAVE）试验中提出了分析氧化损伤的特定生物化学测量（在基线时的所有标记和硝基酪氨酸和氯吡霉素），该试验随机420 38-86岁的女性与先前的心血管疾病事件一起，以供众所周知/c，vite/c Combintation/c Combintation/Combistination/Combistination and Combistination and Combistination and Combistion and Combistination。波浪将确定这些处理对基线时最小冠状动脉直径的定量血管造影评估的功效，并在2001年前10个月内完成的最终访问。我们将从几类化合物中测量氧化产物（通过F2-异丙烷，通过Nitrotrotosine和Chlorotyrosine和Chlorotyrosine和Choromotyrosine和Chorolotyrosine蛋白质的脂质来测量脂质。 8-羟基-2'-脱氧鸟苷），从而研究了可能导致动脉粥样硬化的几种主要途径。此外，用C反应蛋白，P-选择蛋白的血小板激活，脂质代谢改变了脂质谱的改变，研究人群的其他特征将整合到波浪中氧化损伤的评估中。通过测量这些各种因素并评估几类化合物中的氧化损伤，我们可以测试氧化损伤的特定途径之间的关系，补充Vite/C和/或HRT以及其他危险因素以及已建立的大型血管疾病的发展。