SUPERFUND CHEMICALS, NUTRITION, ENDOTHELIAL CELL DYSFUNCTION

SUPERFUND 化学品、营养、内皮细胞功能障碍

• 批准号: 6457648
• 负责人: BERNHARD HENNIG
• 金额: $ 14.25万
• 依托单位: UNIVERSITY OF KENTUCKY
• 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 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6457648
• 关键词: atherosclerosis; cytotoxicity; dietary lipid; environmental toxicology; gene targeting; genetically modified animals; halobiphenyl /halotriphenyl compound; hazardous substances; human tissue; laboratory mouse; laboratory rabbit; nutrition related tag; oxidative stress; toxin metabolism; vascular endothelium

There is evidence that exposure to certain Superfund chemicals (e.g., PCBs) can be implicated in the development of cardiovascular diseases such as atherosclerosis. Studies also suggest that high-fat diets are associated with a high risk of heart and blood vessel diseases. Because of similar lipolytic properties, the cytotoxicity of PCBs may be influenced by the type of dietary dat that is being consumed. Our preliminary evidence suggests that oxidative stress is a critical event in PCB-mediated endothelial cell dysfunction. Because of its constant exposure to blood components, including environmental contaminants, pro-oxidants, stress and dysfunction. Thus, it is very likely that certain diet-derived fats, especially unsaturated fats, can greatly alter the cellular lipid and oxidant/antioxidant environment and thus further compromise the PCB- mediated endothelial integrity. A major focus of the present proposal will be to test the hypothesis that specific dietary fats can potentiate PCB- mediated endothelial cell dysfunction and that specific nutrient interventions, such as increasing the intake of antioxidant nutrients/chemicals (e.g., vitamin E and glutathione precursors), can provide protection against PCB/lipid-mediated atherosclerosis. To test this hypothesis, we will study he commercially available saturated and polyunsaturated fat sources. Because diet-derived lipids are carried and packaged in the blood as lipoproteins, it also will be necessary to feed animals (rabbits) diet enriched with the above mentioned fats and study the effects of lipoproteins derived from these animals on PCB- compromised endothelial cell integrity. Finally, an ApoE knock-out mouse model, which mimics the pathology of human atherosclerosis, will be utilized to correlate the effects of dietary dat and PCBs on atherogenic markers of endothelial cell dysfunction. Results from this work will provide valuable information towards therapeutic nutrition intervention for populations at or near Superfund sites.

有证据表明，暴露于某些超级基金化学物质（例如，PCB）可能与心血管疾病（如动脉粥样硬化）的发展有关。研究还表明，高脂饮食与心脏和血管疾病的高风险有关。由于具有类似的脂解特性，PCB的细胞毒性可能受到所消耗的饮食DAT的类型影响。我们的初步证据表明，氧化应激是PCB介导的内皮细胞功能障碍中的关键事件。由于它不断暴露于血液成分，包括环境污染物，促氧化剂，应力和功能障碍。因此，某些饮食来源的脂肪很可能会大大改变细胞脂质和氧化剂/抗氧化剂的环境，从而进一步损害PCB介导的内皮完整性。本提案的主要重点是检验以下假设：特定饮食脂肪可以增强PCB介导的内皮细胞功能障碍以及特定的营养干预措施，例如增加抗氧化剂/化学物质的摄入量（例如，维生素E和粘性前体），可以为PCB/LIPIDS提供保护。为了检验这一假设，我们将研究他在市售饱和和多不饱和的脂肪来源。由于饮食来源的脂质被作为脂蛋白携带并包装在血液中，因此也有必要喂养富含上述脂肪的动物（兔子）饮食，并研究源自这些动物对PCB的脂蛋白对PCB-折衷的内皮细胞完整性的影响。最后，模仿人动脉粥样硬化的病理的ApoE敲除小鼠模型将用于将饮食DAT和PCB对内皮细胞功能障碍的动脉粥样硬化标记的影响相关联。这项工作的结果将为超级基金站点或附近人口的治疗营养干预提供宝贵的信息。