SUPERFUND CHEMICALS AND ENDOTHELIAL CELL DYSFUNCTION
SUPERFUND 化学品和内皮细胞功能障碍
基本信息
- 批准号:6217743
- 负责人:
- 金额:$ 19.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-04-01 至 2000-03-31
- 项目状态:已结题
- 来源:
- 关键词:antiatherogenic agent antioxidants atherosclerosis calcium metabolism carbopolycyclic compound cardiovascular disorder cytochrome P450 cytotoxicity environmental toxicology halobiphenyl /halotriphenyl compound lipid metabolism oxidizing agents tissue /cell culture toxin metabolism vascular endothelium vascular endothelium permeability
项目摘要
Polyhalogenated aromatic hydrocarbons (e.g. PCBs) and polycyclic
aromatic hydrocarbons (e.g., BP) have been implicated in the
atherosclerotic disease process. Even though mechanisms of the
atherogenic potential of these environmental contaminants are not
known, critical events of cell dysfunction may occur at the
endothelial cell level. The vascular endothelium 'communicates'
with blood-borne cells and abluminal tissues and acts as a barrier to
the movement of plasma components (e.g., cholesterol-rich
lipoproteins) from the blood to the arterial wall. Cell injury, or any
event which disrupts endothelial integrity and thus endothelia
permeability properties, may be involved in the early events leading
to atherosclerotic lesion formation. We propose that aromatic
hydrocarbons are atherogenic by causing cell dysfunction and a
subsequent disruption of endothelial barrier function. We
hypothesize that these events are mediated by 1) alteration in lipid
profile and lipid metabolism, 2) cytochrome P-450 1A1 induction, 3)
increased oxidative stress, 4) DNA adduct formation and oxidative
DNA damage, and 5) alteration of calcium metabolism. Thus, the
extent of the movement of atherogenic lipoprotein remnants across
and into the arterial wall may be directly correlated to the severity of
endothelial cell barrier function disruption. We also hypothesize that
diet-derived fats, i.e., fatty acids differing in carbon length and
degree of unsaturation, can greatly alter the cellular lipid and
oxidant/antioxidant environment and thus influence the aromatic
hydrocarbon-mediated cell dysfunction. Furthermore, this research
will explore mechanisms by which certain nutrients or chemicals
having antioxidant or membrane stabilizing properties, may protect
the endothelium from aromatic hydrocarbon-induced cell injury. Porcine-
and human-derived endothelial cells will be cultured and used in the
proposed research. First, a series of studies will be conducted to
determine mechanisms of aromatic hydrocarbon-mediated endothelial
cell dysfunction. In the second phase, the interactive events of
certain lipids and aromatic hydrocarbons on endothelial cell
metabolism will be explored. During the third phase, a series of
studies will be undertaken to determine the mechanisms by which
selected nutritional interventions in culture may protect agonist cell
injury under the conditions cited above. Results of the proposed
studies should identify mechanisms of Superfund Chemical-mediated
endothelial cell dysfunction and their implication in atherosclerosis.
多卤代芳烃(例如 PCB)和多环
芳香烃(例如 BP)与
动脉粥样硬化疾病过程。 尽管机制
这些环境污染物的致动脉粥样硬化潜力并不
已知,细胞功能障碍的关键事件可能发生在
内皮细胞水平。 血管内皮“沟通”
与血源性细胞和管腔组织结合,并充当屏障
血浆成分(例如富含胆固醇的物质)的运动
脂蛋白)从血液到动脉壁。 细胞损伤或任何
破坏内皮完整性从而破坏内皮的事件
渗透性特性,可能与导致的早期事件有关
至动脉粥样硬化病变的形成。 我们建议芳香
碳氢化合物会导致细胞功能障碍,从而导致动脉粥样硬化
随后破坏内皮屏障功能。 我们
假设这些事件是由 1) 脂质改变介导的
概况和脂质代谢,2) 细胞色素 P-450 1A1 诱导,3)
氧化应激增加,4) DNA 加合物形成和氧化
DNA 损伤,5) 钙代谢的改变。 因此,
致动脉粥样硬化脂蛋白残余物的移动程度
并进入动脉壁可能与严重程度直接相关
内皮细胞屏障功能破坏。 我们还假设
饮食来源的脂肪,即碳长度不同的脂肪酸
不饱和度,可以极大地改变细胞脂质和
氧化剂/抗氧化剂环境,从而影响芳香族
碳氢化合物介导的细胞功能障碍。 此外,这项研究
将探索某些营养素或化学物质的机制
具有抗氧化或膜稳定特性,可以保护
芳香烃引起的细胞损伤的内皮细胞。 猪-
人源内皮细胞将被培养并用于
提出的研究。 首先,将进行一系列研究
确定芳香烃介导的内皮细胞的机制
细胞功能障碍。 第二阶段的互动活动
内皮细胞上的某些脂质和芳香烃
将探索新陈代谢。 在第三阶段,一系列
将进行研究以确定机制
培养中选定的营养干预措施可以保护激动细胞
在上述情况下受伤。 提议的结果
研究应确定超级基金化学介导的机制
内皮细胞功能障碍及其在动脉粥样硬化中的意义。
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:
$ 19.85万 - 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:
$ 19.85万 - 项目类别:
Superfund Chemicals Nutrition and Endothelial Cell Dysfu
超级基金化学品营养与内皮细胞失调
- 批准号:
6932244 - 财政年份:2005
- 资助金额:
$ 19.85万 - 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:
$ 19.85万 - 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:
$ 19.85万 - 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:
$ 19.85万 - 项目类别:
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