TOBACCO SMOKE COMPONENTS AND ATHEROSCLEROSIS

烟草烟雾成分与动脉粥样硬化

• 批准号: 3343514
• 负责人: NANCY JEAN HALEY
• 金额: $ 9.62万
• 依托单位: NAYLOR DANA INSTITUTE FOR DISEASE PREV
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3343514
• 关键词: aorta; atherosclerosis; benzopyrenes; carbon monoxide; cholesterol; disease /disorder proneness /risk; electron microscopy; gas chromatography; histochemistry /cytochemistry; histopathology; nicotine; nitrosamines; postmortem; radioimmunoassay; tobacco; toxin metabolism; vascular endothelium

Cigarette smoking is a major contributing factor for the development of cardiovascular diseased including atherosclerosis. It induces also a hightly complex pharmacological action, primarily because each smoker inhales with the smoke aerosol more than 3,800 compounds many times each day. Several of these compounds have been associated with accelerated atherogenesis, but as yet, demonstration of disease similar to that seen in humans has not been verified in animals in response to individual smoke constitutents, or to the total inhaled smoke. It is the aim of this proposal to initiate such an investigation and to identify fractions of tobacco smoke which might exert atherogenic effects on the arterial wall. We will extend and characterize our preliminary observations (included herein) on the development of atherosclerosis in Syrian golden hamsters exposed to mainstream smoke for 18 months. Specifically, through histological, morphological and biochemical methods, we proposed to analyze aortic tissue derived from controls and from animals exposed to smoke fractions, as well as total mainstream smoke, and to determine the extent of plaque formation in response to the isolated risk factor of cigarette smoking. Increased atheroscherosis has been demonstrated at autopsy in human cigarette smokers, but assignment of relative risk can be made only with animal bioassays where cause and effect relationships can be tested. We will conduct our studies in Syrian golden hamsters, a well established animal model for smoke exposure. They are tolerant of the smoking regimes, have circulating lipid levels similar to humans and respond to tobacco-specific carcinogens. In addition, our preliminary results demonstrate that these animals develop biochemical markers of atherosclerosis during long-term exposure to mainstream cigarette smoke. The fractions present in cigarette smoke which exert atherogenic effects remain to be elucidated. With consideration of the changing cigarette product, this research is essential in determining relative risks of various cigarette yields and for developing concepts for reducing cardiovascular risks.

吸烟是发展中国家的一个主要因素。 心血管疾病，包括动脉粥样硬化。 它也导致了一个 非常复杂的药理作用，主要是因为每个吸烟者 每次吸入烟雾中的3,800多种化合物 天 其中几种化合物与加速 动脉粥样硬化，但迄今为止，疾病的表现类似于在 人类尚未在动物中验证对单个烟雾的反应 或总吸入烟雾。 本提案的目的是启动此类调查， 鉴定烟草烟雾中可能产生致动脉粥样硬化作用的组分 在动脉壁上 我们将扩展和描述我们的初步 观察（包括在此）动脉粥样硬化的发展， 叙利亚金仓鼠暴露在主流烟雾中18个月。 具体来说，通过组织学、形态学和生物化学方法， 我们建议分析来自对照组和动物的主动脉组织， 暴露于烟雾成分，以及总的主流烟雾， 确定斑块形成的程度，以应对孤立的风险 吸烟的因素。 动脉粥样硬化的增加 在人类吸烟者的尸检中证明，但分配 只有在因果关系 关系可以测试。 我们将在叙利亚金仓鼠中进行研究， 烟雾暴露的动物模型。 他们容忍吸烟制度， 循环脂质水平与人类相似， 烟草特有的致癌物质 此外，我们的初步结果 证明这些动物发展出 动脉粥样硬化在长期暴露于主流香烟烟雾。 香烟烟雾中产生致动脉粥样硬化作用的组分 仍有待阐明。 考虑到香烟的变化 产品，这项研究是必不可少的，在确定相对风险 不同的卷烟产量和发展的概念， 心血管风险。