SUPERFUND CHEMICALS, NUTRITION, ENDOTHELIAL CELL DYSFUNCTION

有证据表明，接触某些超级基金化学品（例如，多氯联苯（PCBs）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正在消费的饮食数据类型的影响。我们的初步证据表明，氧化应激是PCB介导的内皮细胞功能障碍的关键事件。因为它不断暴露于血液成分，包括环境污染物，促氧化剂，压力和功能障碍。因此，很可能某些饮食来源的脂肪，特别是不饱和脂肪，可以极大地改变细胞脂质和氧化剂/抗氧化剂环境，从而进一步损害PCB介导的内皮完整性。本提案的一个主要重点是检验以下假设：特定的膳食脂肪可以增强PCB介导的内皮细胞功能障碍，特定的营养干预，如增加抗氧化营养素/化学品的摄入（例如，维生素E和谷胱甘肽前体），可以提供对PCB/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脂肪和多不饱和脂肪来源。由于饮食来源的脂质作为脂蛋白携带并包装在血液中，因此也有必要给动物（兔）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受损的内皮细胞完整性的影响。最后，一个ApoE基因敲除小鼠模型，它模仿人类动脉粥样硬化的病理，将被用来关联的饮食数据和多氯联苯对内皮细胞功能障碍的致动脉粥样硬化标志物的影响。这项工作的结果将提供有价值的信息，对治疗营养干预的人口或附近的超级基金网站。

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.