Project 1: Cardiovascular Toxicity of Tobacco Products
Sanjay Srivastava, Ph.D.
(University of Louisville)
- Examine tobacco-induced endothelial injury. To examine tobacco-induced endothelial injury: In adult mice exposed to varying intensities of tobacco smoke and smokeless tobacco, we will identify urinary metabolites of tobacco-derived aldehydes and determine how these relate to the extent and duration of exposure. We will also determine how these markers are affected by gender, time, and duration of exposure. We will identify specific indices of endothelial function and damage that robustly and sensitively reflect endothelial injury and thrombosis, as well as how these biomarkers of injury are related to the biomarkers of exposure.
- Delineate the contribution of harmful and potentially harmful (HPHC) constituents, such as aldehydes, to endothelial injury induced by tobacco exposure. To identify which constituents of tobacco and tobacco smoke contribute to endothelial damage, we will examine changes in the biomarkers of endothelial injury in mice exposed to individual constituents of exposure: nicotine, acrolein and crotonaldehyde. We will determine how removing them affects endothelial injury due to tobacco smoke and whether increases in the extent of exposure to these aldehydes and related reactive chemicals increases the extent of endothelial injury.
Project 2: Cardiovascular Injury Due to Tobacco Use
Aruni Bhatnagar, Ph.D.
(AHA, University of Louisville)
- Elucidate the relationship between biomarkers of cardiovascular injury and exposure to tobacco smoke and smokeless tobacco. We will evaluate biomarkers of endothelial damage and predilection for thrombosis in a cohort of 480 smokers, smokeless tobacco users and non-smokers without overt CVD. We will determine how these biomarkers are associated with the extent and duration of exposure to tobacco constituents.
To assess injury, we will measure endothelial vasodilator function, arterial stiffness, endothelium-derived microparticles, endothelial progenitor cells (EPCs), and changes in thrombosis. Exposure will be evaluated by measuring the urinary metabolites of nicotine and tobacco and tobacco-smoke derived aldehydes.
- Identify and compare the dose-dependent associations between tobacco exposure, measures of subclinical cardiovascular disease, and clinical cardiovascular events. Using data from the Multi-Ethnic Study of Atherosclerosis (MESA) prospective cohort, we will examine associations between tobacco exposure and subclinical vascular disease as assessed by carotid intima-media thickness, coronary artery calcification, ankle brachial index, flow mediated dilation and arterial stiffening, and biomarkers of inflammation.
We will also investigate the influence of tobacco exposure on progression of subclinical CVD surrogates in longitudinal assessments. These data will be analyzed after stratification by age, gender, race/ethnicity and medication use. We will also elucidate the nature of the interaction between tobacco exposure, subclinical cardiovascular injury and subsequent 10-year cardiovascular events as well as total mortality.
- Validate candidate biomarkers associated with tobacco exposure in independent human cohorts. Candidate bio-measures reflective of tobacco-induced cardiovascular injury, identified in Aims 1 and 2 will be independently validated in The Jackson Heart Study (JHS) cohort and assessed for their association with urinary metabolites of nicotine and aldehydes.
To determine the relationship between biomarkers of endothelial injury and tobacco exposure identified in Aim 1 that cannot be measured in banked samples, we will seek to conduct testing on baseline banked samples in the MESA cohort and/or the emerging ELSA-Brazil cohort and procure additional samples for the analysis of candidate biomarkers that cannot be evaluated in banked samples.
Project 3: Perception of Tobacco Use in Vulnerable Populations
Thomas J. Payne, Ph.D.
(University of Mississippi Medical Center)
We will examine channel use frequency (i.e., what are the most frequent channels for seeking tobacco-related communication and what are the most frequent channels for communicating with others about tobacco?) and the influence of several factors that modify these choices. For example, modifying factors will include age, gender, race, knowledge about tobacco, tobacco use or intention, family tobacco use and peer tobacco use?
Aim: To document communication methods for tobacco use, knowledge, risk perception and intention and determine the effect of socio-economic status, gender, age group and race on these outcomes.