Project 5: Cardiovascular Assessment ofthe Effects of Tobacco and Nicot p341-385

项目 5：烟草和尼古特影响的心血管评估 p341-385

• 批准号: 8592287
• 负责人: PETER GANZ
• 金额: $ 44.1万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-19 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8592287
• 关键词: Affect; Arteries; Autonomic nervous system; Biological Markers; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cigarette; Clinical; Coagulation Process; Data; Electronics; Exposure to; Goals; Human; Individual; Inflammation; Instruction; Modeling; Molecular; Nicotine; Outcome Study; Oxidative Stress; Particulate Matter; Physiological; Play; Regulation; Relative (related person); Research; Risk; Role; Safety; Smokeless Tobacco; Testing; Thrombosis; Tobacco; Tobacco use; Toxin; Vascular Endothelium; base; cardiovascular disorder risk; cardiovascular risk factor; cigarette smoking; environmental tobacco smoke; human subject; improved; particle; vapor

Cigarette smoking continues to be a major cause of cardiovascular disease (CVD). In contrast, the cardiovascular risks of other tobacco products in common use (smokeless tobacco) and new tobacco products (e-cigarettes) are not adequately understood. The FDA will need information about the cardiovascular safety of these products to inform their regulatory decisions. While long-term clinical outcome studies that investigate the cardiovascular risks of tobacco products would be optimal, they take too long to provide the data that the FDA needs now. Disturbances in the function of vascular endothelium (the lining of arteries, which plays an important role in regulating vascular function), in the activation ofthe autonomic nervous system and increased inflammation, oxidative stress and propensity to thrombosis (clotting) are key mechanisms in the progression of CVD and provide useful and validated biomarkers of CVD risk. These biomarkers form the basis for our model to assess the CVD risks of tobacco product use and secondhand smoke exposure. We will conduct controlled, short-term exposures of human subjects to test products that provide a wide range of nicotine, particle and other cardiovascular toxin concentrations to determine how these components associated with tobacco use adversely affect cardiovascular risk. Specifically, we will 1) determine the relative contributions of nicotine and combustion products to the cardiovascular risk of active cigarette smoking; 2) determine which cardiovascular risk biomarkers are affected by exposure to low concentrations of secondhand smoke; 3) determine the cardiovascular risk of smokeless tobacco use; and 4) determine the cardiovascular risk of electronic cigarettes and the respective contributions of nicotine and electronic cigarette vapor. By quantifying and comparing the immediate effects of 4 different kinds of tobacco products on the cardiovascular system. Project 5 will validate a sensitive and practical panel of physiological and molecular biomarkers that predict cardiovascular disease and will be of great use in premarket human testing of tobacco products. C RELEVANCE (See instructions): Our research will provide information as to how individual key components of tobacco and nicotine delivery products, i.e. nicotine, particulate matter, and other cardiovascular toxins, affect cardiovascular risk and if smokeless tobacco and e-cigarettes pose cardiovascular risks. Ultimately, our biomarker model will serve as a cardiovascular safety screen for the FDA in its oversight of conventional, new, and emerging tobacco products.

吸烟仍然是心血管疾病（CVD）的主要原因。而反观 其他常用烟草制品（无烟烟草）和新烟草的心血管风险 产品（电子烟）尚未得到充分了解。FDA将需要有关 这些产品的心血管安全性，以告知他们的监管决策。虽然长期临床结果 调查烟草制品的心血管风险的研究将是最佳的，他们需要太长的时间， 提供FDA现在需要的数据。血管内皮（血管内膜）功能紊乱 在调节血管功能中起重要作用的动脉），在自主神经的激活中 神经系统和炎症增加，氧化应激和血栓形成（凝血）的倾向是关键 这些研究揭示了CVD进展的机制，并提供了CVD风险的有用和经验证的生物标志物。这些 生物标志物构成了我们模型的基础，以评估烟草制品使用和二手烟草制品的CVD风险。 烟雾暴露。我们将对人类受试者进行受控的短期暴露于测试产品， 提供广泛的尼古丁，颗粒和其他心血管毒素浓度，以确定如何 这些与烟草使用有关的成分对心血管风险有不利影响。具体而言，我们将1） 确定尼古丁和燃烧产物对心血管风险的相对贡献， 吸烟; 2）确定哪些心血管风险生物标志物受到暴露于低浓度的 二手烟浓度; 3）确定无烟烟草使用的心血管风险;以及4） 确定电子香烟的心血管风险以及尼古丁和 电子烟烟雾通过量化和比较4种不同烟草的即时效应， 产品对心血管系统。项目5将验证一个敏感和实用的生理小组， 和预测心血管疾病的分子生物标志物，并将在上市前的人类 烟草制品检测。 C 相关性（参见说明）： 我们的研究将提供有关烟草和尼古丁传递的各个关键成分的信息 产品，即尼古丁，颗粒物和其他心血管毒素，影响心血管风险，如果 无烟烟草和电子烟会带来心血管风险。最终，我们的生物标志物模型将作为 为FDA监督传统、新型和新兴烟草提供心血管安全筛查 产品.