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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

基本信息

批准号：
9186130
负责人：
Michael T Kleinman
金额：
$ 36.69万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
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/9186130
关键词：
Acids Acute Address Adolescent and Young Adult Adverse effects Aerosols Affect Air Aldehydes 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 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 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 cigarette smoking comparative heart rate monitor heart rhythm hookah in vitro Assay in vitro testing in vivo innovation ionization mass spectrometer mouse model particle respiratory response selenol time use toxicant vapor

项目摘要

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.

项目总结