Superfund Chemicals Nutrition and Endothelial Cell Dysfu
超级基金化学品营养与内皮细胞失调
基本信息
- 批准号:6932244
- 负责人:
- 金额:$ 30.37万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-04-01 至 2008-03-31
- 项目状态:已结题
- 来源:
- 关键词:antiatherogenic agentantioxidantsatherosclerotic plaquebiological signal transductioncarbopolycyclic compoundcaveolascaveolinsdietary constituentenvironmental toxicologyfatty acid transporthalobiphenyl /halotriphenyl compoundhuman tissueinflammationlaboratory mousenutrient interactionnutrition related tagpathologic processperoxisome proliferator activated receptortissue /cell culturetoxicant interactionvascular endothelium
项目摘要
Atherosclerosis, a chronic inflammatory disease, is still the number one cause of death in the United States. Numerous risk factors for the development of atherosclerosis have been identified, including obesity and hypertriglyceridemia. Superfund chemicals such as PHAs and PCBs also have been shown to increase the risk and incidence of cardiovascular diseases. Most of all, we have evidence that both selected PCBs and fatty acids can induce endothelial cell dysfunction and inflammation, critical events in the early pathology of atherosclerosis. Little is known about mechanisms and regulation of cellular uptake, trafficking and initiation
of proinflammatory pathways by both PCBs and fatty acids. Membrane lipid rafts such as caveolae are particularly abundant in endothelial cells, where they are believed to play a major role in the regulation of endothelial vesicular trafficking. Thus, we hypothesize that caveolae are critical in the cellular uptake of fatty acids and lipophilic environmental contaminants such as PCBs. More recently, caveolae have also been implicated in the regulation of cell signal transductions. Thus, we hypothesize that PCBs and certain fatty acids interact with caveolae and trigger distinct proatherogenic signaling pathways, leading to endothelial cell dysfunction. We also hypothesize that these signaling pathways can be down-regulated by antioxidant
nutrients and related bioactive compounds as well as by ligands of antiatherogenic nuclear receptors (PPARs). These hypotheses will be tested in vitro as well as in vivo by studying the interactions of PCBs with dietary compounds such as fatty acids and antioxidants. Importantly, we will use cell and mouse models lacking the caveolin gene to determine the involvement of caveolae in the PCB and fatty acid uptake and toxicity. We propose to explore mechanisms of nutrient-mediated modulation of PCB toxicity, and the outocome of our proposed study may lead to novel nutritional recommendations and therapeutic interventions in population exposed to Superfund chemicals.
动脉粥样硬化,一种慢性炎症性疾病,仍然是美国的头号死因。许多动脉粥样硬化发展的危险因素已被确定,包括肥胖和高脂血症。超级基金化学品,如PHA和PCB,也被证明会增加心血管疾病的风险和发病率。最重要的是,我们有证据表明,选定的多氯联苯和脂肪酸都可以诱导内皮细胞功能障碍和炎症,这是动脉粥样硬化早期病理学中的关键事件。关于细胞摄取、运输和启动的机制和调控知之甚少
多氯联苯和脂肪酸的促炎途径。膜脂筏如小窝在内皮细胞中特别丰富,据信它们在调节内皮囊泡运输中起主要作用。因此,我们假设,小窝是至关重要的脂肪酸和亲脂性环境污染物,如多氯联苯的细胞摄取。最近,小窝也参与了细胞信号转导的调节。因此,我们假设多氯联苯和某些脂肪酸与小窝相互作用,并触发不同的促动脉粥样硬化信号通路,导致内皮细胞功能障碍。我们还假设这些信号通路可以被抗氧化剂下调,
营养素和相关的生物活性化合物以及抗动脉粥样硬化核受体(PPARs)的配体。这些假设将通过研究多氯联苯与膳食化合物(如脂肪酸和抗氧化剂)的相互作用,在体外和体内进行测试。重要的是,我们将使用缺乏小窝蛋白基因的细胞和小鼠模型来确定小窝在PCB和脂肪酸摄取和毒性中的参与。我们建议探索营养介导的PCB毒性调节机制,我们提出的研究结果可能会导致新的营养建议和治疗干预暴露于超级基金化学品的人群。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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BERNHARD HENNIG其他文献
BERNHARD HENNIG的其他文献
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{{ truncateString('BERNHARD HENNIG', 18)}}的其他基金
Project 1: Superfund Chemicals Nutrition and Endothelial Cell Dysfunction
项目1:超级基金化学品营养与内皮细胞功能障碍
- 批准号:
8249960 - 财政年份:2011
- 资助金额:
$ 30.37万 - 项目类别:
Project 1: Superfund Chemicals Nutrition and Endothelial Cell Dysfunction
项目1:超级基金化学品营养与内皮细胞功能障碍
- 批准号:
8053921 - 财政年份:2010
- 资助金额:
$ 30.37万 - 项目类别:
SUPERFUND CHEMICALS, NUTRITION, ENDOTHELIAL CELL DYSFUNCTION
SUPERFUND 化学品、营养、内皮细胞功能障碍
- 批准号:
6630568 - 财政年份:2002
- 资助金额:
$ 30.37万 - 项目类别:
SUPERFUND CHEMICALS, NUTRITION, ENDOTHELIAL CELL DYSFUNCTION
SUPERFUND 化学品、营养、内皮细胞功能障碍
- 批准号:
6457648 - 财政年份:2001
- 资助金额:
$ 30.37万 - 项目类别:
SUPERFUND CHEMICALS, NUTRITION, ENDOTHELIAL CELL DYSFUNCTION
SUPERFUND 化学品、营养、内皮细胞功能障碍
- 批准号:
6301507 - 财政年份:2000
- 资助金额:
$ 30.37万 - 项目类别:
SUPERFUND CHEMICALS AND ENDOTHELIAL CELL DYSFUNCTION
SUPERFUND 化学品和内皮细胞功能障碍
- 批准号:
6217743 - 财政年份:1999
- 资助金额:
$ 30.37万 - 项目类别:
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