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Cardiovascular Toxicity of Tobacco Products and Constituents

Principal Investigator: Daniel J. Conklin

Funding Mechanism: National Institutes of Health - Grant

ID number: 1 R01 HL122676-01A1

Award Date: 7/6/2015

Institution: University of Louisville

Tobacco product use is associated with increased risk of cardiovascular disease. The goals of this project are to quantify and evaluate the cardiovascular toxicity of the major aldehydes in tobacco products and to validate the association between exposure to these aldehydes and cardiovascular toxicity in humans. Specific aims are: (1) to assess the contribution of aldehydes to the cardiovascular toxicity of tobacco products in mice; (2) to evaluate the cardiovascular toxicity of individual aldehydes and the toxicity modification by nicotine in mice; and (3) to identify aldehyde-induced cardiovascular toxicity in humans. To address Aim 1, researchers will conduct acute and chronic inhalation studies to expose adult male mice to cigarette smoke containing variable levels of acetaldehyde, acrolein, and formaldehyde (which are classified by the FDA as harmful and potentially harmful constituents [HPHCs]) within the range of commercially-available cigarettes or e-cigarette aerosols and evaluate cardiovascular risk factors, including changes in thrombosis, insulin resistance, and plasma lipids. To address Aim 2, researchers will expose adult male mice to different levels of individual aldehydes to determine the dose-response relationship between aldehyde exposure and cardiovascular injury; they will also examine how the presence of nicotine affects aldehyde toxicity and metabolism, and whether dual exposure to tobacco smoke and e-cigarette aerosol results in increased cardiovascular toxicity. To address Aim 3, researchers will use banked blood and urine samples from 350 high-risk cardiovascular disease patients (adult smokers and nonsmokers over age 21 already enrolled in the Louisville Healthy Heart Study) to evaluate whether the cardiovascular toxicity profiles in human smokers are comparable to patterns of aldehyde-induced toxicity in mice. Study findings will provide information about how major aldehydes present in cigarette smoke and e-cigarette aerosols contribute to cardiovascular toxicity.

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