SUPERFUND CHEMICALS, NUTRITION, ENDOTHELIAL CELL DYSFUNCTION

有证据表明，接触某些超级基金化学品(如多氯联苯)可能与动脉粥样硬化等心血管疾病的发展有关。研究还表明，高脂肪饮食与心脏和血管疾病的高风险有关。由于类似的脂肪分解特性，多氯联苯的细胞毒性可能会受到所消费的饮食数据类型的影响。我们的初步证据表明，氧化应激在多氯联苯介导的内皮细胞功能障碍中是一个关键事件。因为它经常暴露在血液成分中，包括环境污染物、促氧化剂、压力和功能障碍。因此，某些饮食来源的脂肪，特别是不饱和脂肪，很可能会极大地改变细胞的脂质和氧化/抗氧化环境，从而进一步损害多氯联苯介导的内皮完整性。本提案的主要重点将是检验这样一种假设，即特定的膳食脂肪可以加强多氯联苯介导的内皮细胞功能障碍，以及特定的营养干预措施，如增加抗氧化营养素/化学物质(例如，维生素E和谷胱甘肽前体)的摄入量，可以提供对多氯联苯/脂质介导的动脉粥样硬化的保护。为了验证这一假设，我们将研究商业上可用的饱和和多不饱和脂肪来源。由于饮食衍生的脂类在血液中以脂蛋白的形式携带和包装，因此也有必要喂养富含上述脂肪的动物(兔)饮食，并研究这些动物衍生的脂蛋白对多氯联苯损害的内皮细胞完整性的影响。最后，模拟人类动脉粥样硬化病理的载脂蛋白E基因敲除小鼠模型将被用来关联饮食dat和多氯联苯对内皮细胞功能障碍的动脉粥样硬化标记物的影响。这项工作的结果将为超级基金站点或附近人群的治疗性营养干预提供有价值的信息。

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.