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生有关。研究还表明，高脂肪饮食与患心脏和血管疾病的高风险有关。由于多氯联苯具有类似的溶脂特性，其细胞毒性可能受到所食用的饮食数据类型的影响。我们的初步证据表明，氧化应激是多氯联苯介导的内皮细胞功能障碍的关键事件。因为它经常暴露于血液成分，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。本研究的主要重点是验证以下假设：特定的膳食脂肪可以增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，如增加抗氧化营养素/化学物质（如维生素E和谷胱甘肽前体）的摄入，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，我们将研究市售的饱和和多不饱和脂肪来源。由于饮食来源的脂质以脂蛋白的形式携带和包装在血液中，因此也有必要给动物（兔子）喂食富含上述脂肪的饮食，并研究来自这些动物的脂蛋白对PCB受损内皮细胞完整性的影响。最后，一个模拟人类动脉粥样硬化病理的ApoE敲除小鼠模型，将被用于将饮食数据和多氯联苯对内皮细胞功能障碍的动脉粥样硬化标志物的影响联系起来。这项工作的结果将为在超级基金站点或其附近的人群提供有价值的营养干预治疗信息。

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.