Cardiovascular Toxicity of Tobacco Products The Family Smoking Prevention and Tobacco Control Act grants the FDA the authority to regulate tobacco products to protect public health. However, to set standards for tobacco products, it is important to know which components of conventional, new and emerging tobacco products induce cardiovascular injury so as to provide toxicity thresholds for harmful and potentially harmful constituents (HPHC) in tobacco products. However, to identify HPHC toxicity, it is important to determine how this toxicity could be identified and associated with disease risk and what assays best compare the toxic properties of different tobacco products. Although for toxicological profiling a high-throughput in vitro method is preferable, CVD is a complex disease that develops from the dysfunction of several organ systems. Therefore, the cardiovascular toxicity of tobacco products cannot be estimated in simple in vitro systems. Hence, we will use an animal model and determine the relative toxicity of major HPHCs in cigarette smoke and electronic cigarette aerosol, determine the toxicity profile of individual HPHCs, specifically aldehydes, and assess how the toxicity of an individual HPHC is modified by other HPHCs and nicotine. To validate this toxicity profile in humans, we will examine the relationship between exposure to different HPHCs and cardiovascular toxicity in a well-characterized cohort. Successful completion of this project will lead to quantitative and rigorous evaluation of the cardiovascular toxicity of the major HPHCs in tobacco products and to the validation of an association between exposure to individual HPHCs and cardiovascular toxicity in humans. These findings will provide new information regarding the contribution of individual aldehydes in HPHC mixtures to the cardiovascular toxicity of tobacco smoke and, as such, will be useful in developing informed threshold limits and the policies needed to regulate HPHC levels in cigarettes, electronic cigarettes, smokeless tobacco as well as in other emerging tobacco-derived products.
Cardiovascular Toxicity of Tobacco Products Project Narrative Although the rates of smoking have declined in the recent past, nearly 1 billion people continue to smoke and cigarette smoking remains the most important cause of preventable deaths worldwide. Smoking and the use of tobacco products are associated with increased risk of developing multiple chronic diseases; however, roughly half of all smoking-related illnesses are due to cardiovascular disease (CVD). Cigarette smoking and potentially the use of smokeless tobacco are associated with an increase in CVD risk factors. Nonetheless, tobacco constituents that mediate the cardiovascular toxicity of tobacco use remain unknown, and therefore, it is unclear how tobacco products could be regulated to reduce cardiovascular injury or how Potential Reduced Exposure Tobacco Products (PREPs) such as electronic cigarettes could be evaluated for cardiovascular toxicity. This project will address this gap in knowledge regarding the toxicity of harmful and potentially harmful constituents (HPHCs) in tobacco products.
| Jin, Lexiao; Lipinski, Alexandra; Conklin, Daniel J (2018) A Simple Method for Normalization of Aortic Contractility. J Vasc Res 55:177-186 |
| Ogunwale, Mumiye A; Li, Mingxiao; Ramakrishnam Raju, Mandapati V et al. (2017) Aldehyde Detection in Electronic Cigarette Aerosols. ACS Omega 2:1207-1214 |
| Abplanalp, Wesley; DeJarnett, Natasha; Riggs, Daniel W et al. (2017) Benzene exposure is associated with cardiovascular disease risk. PLoS One 12:e0183602 |
| Ogunwale, Mumiye A; Chen, Yizheng; Theis, Whitney S et al. (2017) A novel method of nicotine quantification in electronic cigarette liquids and aerosols. Anal Methods 9:4261-4266 |
| Keith, Rachel J; Riggs, Daniel W; Conklin, Daniel J et al. (2017) Nicotine Metabolism in Adults with Type 2 Diabetes. Nicotine Tob Res : |
| Conklin, Daniel J; Malovichko, Marina V; Zeller, Iris et al. (2017) Biomarkers of Chronic Acrolein Inhalation Exposure in Mice: Implications for Tobacco Product-Induced Toxicity. Toxicol Sci 158:263-274 |
| Conklin, Daniel J; Haberzettl, Petra; Jagatheesan, Ganapathy et al. (2017) Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein. Toxicol Appl Pharmacol 324:61-72 |
| Conklin, Daniel J (2016) Acute cardiopulmonary toxicity of inhaled aldehydes: role of TRPA1. Ann N Y Acad Sci 1374:59-67 |
| Conklin, Daniel J; Haberzettl, Petra; Jagatheesan, Ganapathy et al. (2015) Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice. Toxicol Appl Pharmacol 285:136-48 |
