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 人们认为用水烟管（“水烟”）吸烟的危害小于 吸烟燃烧香烟，健康风险的水管吸烟（WPS）甚至可能大于 抽烟WPS的风险包括不良心血管和肺部影响。许多 WPS中的化合物影响心血管和呼吸系统：心率和血液流速升高 压力与尼古丁和WPS中测量的一氧化碳浓度增加有关。 此外，WPS产生破坏性的活性氧或耗尽含SH的抗氧化剂。不可逆 可能发生氧化应激诱导的肺上皮损伤，并与肺上皮细胞的发病机制有关。 冠状动脉疾病和阻塞性肺病。 我们的总体目标是确定WPS成分和吸烟模式的变化如何影响 气体和尺寸分辨颗粒成分的化学组成及其在 心肺疾病的发展和恶化。我们将具体研究 炎症和氧化应激作为烟草烟雾相关疾病发病机制的作用机制。 我们将使用体外试验和体内吸入暴露与转基因小鼠相结合 模型来量化WPS中存在的特定毒物对心肺系统的不良影响。 我们的总体假设是，接触水烟将与炎症和 在我们的体内小鼠模型中，氧化应激将诱导或加剧心肺反应。我们 我进一步假设，这些关联将是由于半挥发性WPS组件与高 炎症和氧化潜力，且除去这些化合物将减轻副作用。 我们将通过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来生成、采样和量化潜在有害物质 WPS中的成分在一定程度上是不可能的，在早期的研究。 2.评估WPS提取物中气相和颗粒相组分的氧化还原和亲电特性 使用体外系统探索几种潜在的重要作用机制。 3.评估和比较水烟在急性和慢性暴露中对小鼠的心肺毒性 重点是确定炎症和氧化应激在肺、脑和心血管中的作用， 系统使用敏感的动脉粥样硬化倾向的动物模型。 这将是第一个研究，以评估不同的心肺毒性的化学 通过体外和体内测定表征水烟烟雾。这项研究将采用创新的最先进的 遥测，以测量呼吸，心电图模式和心脏功能的变化， 在遗传上易患动脉粥样硬化的小鼠中进行亚慢性和慢性暴露后。