Vapor and particulate phase smoke components and cardiovascular dysfunction

蒸气和颗粒相烟雾成分与心血管功能障碍

• 批准号: 9335870
• 负责人: Michael T Kleinman
• 金额: $ 34.83万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9335870
• 关键词: Acids; Acute; Address; Adolescent and Young Adult; Adverse effects; Aerosols; Affect; Air; Aldehydes; Alpha Cell; Alveolar Macrophages; Animal Model; Animals; Antioxidants; Aorta; Asthma; Atherosclerosis; Attention; Belief; Biological Assay; Biological Markers; Blood; Blood Pressure; Brain; Breathing; Caliber; Carbon Monoxide; Cardiac; Cardiopulmonary; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular system; Cells; Chemicals; Chemistry; Chronic; Chronic Obstructive Airway Disease; Cigarette; Control Animal; Coronary Arteriosclerosis; Development; Disease; Epithelium; Excision; Exposure to; Functional disorder; Gases; Health; Heart Rate; Implant; In Vitro; Inflammation; Inflammatory; Infusion Pumps; Inhalation Exposure; Knowledge; Link; Lipid Peroxidation; Lipid Peroxides; Lung; Lung diseases; Measures; Metals; Methods; Modeling; Molecular; Mus; Nicotine; Oxidation-Reduction; Oxidative Stress; Particle Size; Particulate; Pathogenesis; Pattern; Phase; Production; Property; Pulmonary Heart Disease; Quinones; Rattus; Reactive Oxygen Species; Regimen; Research; Resolution; Respiration; Respiratory System; Risk; Role; Sampling; Smoke; Smoker; Smoking; Standardization; Sulfhydryl Compounds; System; Tars; Telemetry; Testing; Time; Tobacco; Tobacco smoke; Tobacco smoking; Toxic effect; Toxicity Tests; Toxicology; United States; Vascular Diseases; Woman; Youth; addiction; analytical method; base; cardiopulmonary system; cigarette smoking; comparative; heart rate monitor; heart rhythm; hookah; in vitro Assay; in vitro testing; in vivo; innovation; ionization; mass spectrometer; mouse model; particle; public health relevance; respiratory; response; selenol; time use; toxicant; vapor

PROJECT SUMMARY Contrary to the belief that the practice of tobacco smoking by waterpipes (`hookah”) is less harmful than smoking combustion cigarettes, the health risks of waterpipe smoking (WPS) may be even greater than smoking cigarettes. The risks of WPS include adverse cardiovascular and pulmonary effects. Many of the compounds in WPS impact the cardiovascular and respiratory systems: Elevated heart rate and blood pressure has been linked to nicotine and the increased carbon monoxide concentrations measured in WPS. Also, WPS generates destructive reactive oxygen species or depletes SH-containing antioxidants. Irreversible oxidative stress-induced damage of the lung epithelium may occur and has been linked to the pathogenesis of coronary artery disease and obstructive pulmonary disease. Our overall objective is to determine how changes in WPS components and smoking patterns effect the chemical composition of both the gaseous and size-resolved particulate constituents and their role in the development and exacerbation of cardiopulmonary diseases. We will specifically examine the role of inflammation and oxidative stress as mechanisms of action in tobacco smoke-related disease pathogenesis. We will use a combination of in vitro tests and in-vivo inhalation exposures with a genetically modified mouse model to quantify adverse effects on the cardiopulmonary system to specific toxicants present in WPS. Our overarching hypothesis is that exposure to hookah smoking will be associated with inflammation and oxidative stress that will induce or exacerbate cardiopulmonary responses in our in vivo mice model. We further hypothesize that these associations will be due to semi-volatile WPS components with high inflammation and oxidative potential and that removal of these compounds will mitigate the adverse effects. We will test our hypotheses with the following three aims: 1. Use state-of-the-art high resolution analytical methods to generate, sample, and quantify potentially harmful constituents in WPS to a degree that was not possible in earlier studies. 2. Assess the redox & electrophilic properties of gas- and particle-phase components present in WPS extracts using in vitro systems that explore several potentially important mechanisms of action. 3. Assess and compare cardiopulmonary toxicities of hookah smoke in mice in acute and chronic exposures with an emphasis on defining the role of inflammation and oxidative stress in lung, brain and cardiovascular systems using a sensitive, atherosclerosis-prone animal model. This will be among the first studies to evaluate differential cardiopulmonary toxicities of chemically characterized hookah smoke by in vitro and in vivo assays. The study will employ innovative state of the art telemetry to measure changes in respiration, electrocardiographic patterns and cardiac function during and after sub-chronic and chronic exposures in mice that are genetically susceptible to atherosclerosis.

项目摘要 与相信烟斗吸烟的实践（“水烟”）相反，危害不如 吸烟混合物香烟，水管吸烟（WPS）的健康风险可能大于 抽烟。 WPS的风险包括不良心血管和肺部作用。许多 WPS中的化合物影响心血管和呼吸系统：心率升高和血液 压力与尼古丁和WPS中测得的一氧化碳浓度增加有关。 此外，WPS会产生破坏性的活性氧或耗尽含Sh的抗氧化剂。不可逆转 可能发生氧化应激引起的肺上皮损伤，并与 冠状动脉疾病和阻塞性肺部疾病。 我们的总体目标是确定WPS组件的变化和吸烟模式如何影响 气态和大小分辨的特殊一致性的化学组成及其在 心肺疾病的发展和加剧。我们将专门研究 炎症和氧化应激作为烟草烟雾相关疾病发病机理中作用机制。 我们将使用一般修饰的鼠标使用体外测试和体内吸入暴露 量化对心肺系统的不良影响与WPS中存在的特定有毒物质的模型。 我们的总体假设是，接触水烟吸烟将与感染和 在我们的体内小鼠模型中会诱导或加剧心肺反应的氧化应激。我们 进一步假设这些关联将是由于半挥发的WPS组件高 炎症和氧化潜力以及去除这些化合物将减轻不良反应。 我们将以以下三个目标来检验我们的假设： 1。使用最先进的高分辨率分析方法生成，样本和量化潜在有害 在早期研究中构成WPS的程度。 2。评估WPS提取物中存在的气相和粒子相分量的氧化还原和亲电性能 使用探索几种潜在重要作用机理的体外系统。 3。评估和比较急性和慢性暴露的小鼠水烟烟雾的心肺毒性 重点是定义炎症和氧化应激在肺，大脑和心血管中的作用 使用敏感的容易动脉粥样硬化动物模型的系统。 这将是最早评估化学差异心肺毒性的研究之一 通过体外和体内测定法表征了水烟烟雾。该研究将采用创新的艺术状态 遥测以测量呼吸发生变化，心电图模式和心脏功能和心脏功能 在易感动脉粥样硬化的小鼠中，亚智和慢性暴露后。