Tobacco Regulation and Addiction Center (A-TRAC)
The American Heart Association's Tobacco Regulation and Addiction Center (A-TRAC) researches the health effects of existing and emerging tobacco products to provide the FDA with the scientific evidence needed to responsibly regulate these products.
Despite how much we know about the harmful effects of tobacco, more than 1.2 billion people use tobacco and tobacco products worldwide. Nearly 6 million people die prematurely as a direct result of tobacco-related causes.
45.3 million adults smoke in the United States and as a result, smoking kills nearly 443,000 people per year, or roughly 1 in every 5 deaths can be attributed to smoking.
Although smoking is often associated with lung disease and cancer, heart disease is the leading cause of death for people who use tobacco products. To understand the relationship between heart disease and tobacco use, it’s critical to study tobacco products effects on the heart and lung systems. The American Heart Association's Tobacco Research and Addiction Center (A-TRAC) gathers cardiologists, scientists, and toxicologists to investigate the health impacts of existing and emerging tobacco products to inform responsible regulation.
The American Heart Association has convened the University of Louisville and eight other academic institutions across the United States to form the Tobacco Regulation and Addiction Center (A-TRAC). A-TRAC supports development and evaluation of tobacco product regulation in order to protect public health and reduce tobacco-related disease, disability, and death. A-TRAC investigators conduct comprehensive multi-disciplinary research that addresses the FDA’s tobacco research priorities and trains future investigators.A-TRAC has helped to shape the production, marketing, and regulation of tobacco and tobacco-related products since 2013.
ATRAC research investigates the underlying mechanisms of tobacco-induced tissue damage that leads to heart disease, investigates the short and long term health impacts of tobacco use, identifies biomarkers for detecting cardiovascular injury, and identifies effective communication methods for changing perceptions about tobacco use.
A-TRAC research generates scientific evidence of:
- Toxicity of tobacco smoke, aerosol, and other inhaled substances,
- Effects of tobacco products on addiction and abuse,
- Short and long-term health effects of tobacco products,
- Knowledge, attitudes, and behaviors related to tobacco product use,
- Effective communication about the health effects of tobacco products,
- Influence of tobacco marketing, and
- Impact of potential FDA regulatory actions.
Association of Cigarette and Electronic Cigarette Use Behaviors With Levels of Inflammatory and Oxidative Stress Biomarkers Among United States Adults, Path 2013-2014
Tobacco Use Prevalence and Transitions Among Adults With a History of Cardiovascular Disease
E-cigarette Aerosol Exposure Acutely Alters Cardiac Conduction and Autonomic Balance and Induces Arrhythmia in Mice
Effects of Electronic Cigarette Solvents on Endothelial Dysfunction
Acute Use Impairs Vascular Function in Exclusive Juul Users (the Jive Study)
Urinary levels of the acrolein conjugates of carnosine are associated with inhaled toxicants
Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco
Electronic Cigarette Use Prevalence, Associated Factors, and Pattern by Cigarette Smoking Status in the United States From NHANES (National Health and Nutrition Examination Survey) 2013-2014
E-cigarette initiation and associated changes in smoking cessation and reduction: the Population Assessment of Tobacco and Health Study, 2013-2015.
Aldehyde Detection in Electronic Cigarette Aerosols
Environmental Determinants of Cardiovascular Disease
Relationship of cigarette smoking with inflammation and subclinical vascular disease: the Multi-Ethnic Study of Atherosclerosis
Electronic cigarettes: a policy statement from the American Heart Association
Acrolein exposure is associated with increased cardiovascular disease risk
A-TRAC investigators at the 2017 annual meeting in Louisville, Kentucky.
Dr. Aruni Bhatnagar
Aruni Bhatnagar, Ph.D. is the Co-Director of the AHA Tobacco Center for Regulatory Science and the Principal Investigator of ATRAC Project 2. He is Professor of Medicine and Professor of Biochemistry and Molecular Biology at the University of Louisville. Dr. Bhatnagar is a Distinguished University Scholar and Director of the Christina Lee Brown Envirome Institute at the School of Medicine. He was elected a fellow of the American Heart Association in 2005. He is known for his pioneering work on the role of the polyol pathway of glucose metabolism and how it is regulated by nitric oxide. His research interests also include cardiovascular effects of environmental pollutants, atherosclerosis, cardiovascular complications of diabetes, and sepsis.
Dr. Daniel Conklin
Daniel J. Conklin, Ph.D., is a Professor of Medicine in the Division of Cardiovascular Medicine at the University of Louisville Diabetes and Obesity Research Center within the Christina Lee Brown Envirome Institute. Dr. Conklin coordinates the A-TRAC program at the University of Louisville and is the Principal Investigator of Project 1. His research has demonstrated the important role that aldehyde metabolism plays in protecting against cardiovascular target organ injury and disease pathogenesis. Dr. Conklin is an Associate Editor of Toxicology and Applied Pharmacology (2007-present) and Cardiovascular Toxicology (2009-2016), and he is on the Editorial Board of Circulation Research since 2015.
Alex Carll, PhD
Alex Carll is an investigator working on the Cardiovascular Toxicity of Tobacco Products project (Project 1). He is Assistant Professor in the Department of Physiology at the University of Louisville. Over the past twelve years, he has investigated the adverse cardiovascular effects of inhaled environmental agents in animals to add biological plausibility to epidemiologic research and inform public health policy. The Carll laboratory studies the biological mechanisms by which air pollutants weaken the heart, impair cardiac conduction, and compromise hemodynamics, and whether such effects occur through the autonomic nervous system.
Andrew P. DeFilippis, MD, ScM
Andrew DeFilippis is leading the Louisville site of the Cardiovascular effects of tobacco products in community-based cohorts (Project 3). He is a Cardiologist and Associate Professor of Medicine in the Division of Cardiovascular Medicine at the University of Louisville, and an Adjunct Assistant Professor of Medicine at Johns Hopkins University. He studies the development of biomarkers of atherosclerosis and has expertise in cohort development, proteomics, lipidomics and metabolomics as powerful tools for biomarker discovery.
Joy L. Hart, PhD
Joy Hart is a senior investigator in the Cardiovascular Injury Due to Tobacco Use (Project 2) and the Cardiovascular effects of tobacco products in community-based cohorts (Project 3) projects. Dr. Hart is Professor in the Department of Communication at the University of Louisville. Her primary interests are in health and organizational communication, particularly in message production and interpretation as well as links to healthy workplaces and lifestyles.
Rachel J. Keith, MSN, PhD
Rachel Keith is a key investigator in the Louisville team of researchers working on the Cardiovascular Injury due to Tobacco Use study (Project 2). She is an Assistant Professor of Medicine at the University of Louisville. Her research and clinical experience have been focused on studying prevention of cardiovascular disease and novel identifiers of early disease.
Matthew A. Nystoriak, PhD
Matt Nystoriak is a part of the Louisville team working on the Cardiovascular Toxicity of Tobacco Products project (Project 1). Dr. Nystoriak is Assistant Professor of Medicine at the University of Louisville. His research has been focused on cellular electrophysiological and functional assays to examine cell membrane potential and transmembrane ion channel activity.
Timothy O’Toole, PhD
Timothy O'Toole is a part of the Bioanalytic and Biomarker Core research team. He is an Assistant Professor of Medicine and a part of the in the Diabetes and Obesity Center at the University of Louisville. His research interests focus on the function and regulation of the endothelium in various disease states and his studies have looked into the effects of diabetes and pollutant exposures on cardiovascular and hematopoietic outcomes including progenitor cell number and function, immune cell responses and platelet function.
Shesh Rai, PhD
Shesh Rai is a senior biostatistician and co-investigator in the Center’s Administrative Core. Dr. Rai is a Fellow of the American Statistical Association, the Wendell Cherry Chair in Clinical Trial Research at the University of Louisville and a Professor of Bioinformatics and Biostatistics. He is also the Director of the Biostatistics Shared Facility at the James Graham Brown Cancer Center. He has more than 13 years of experience designing pre-clinical, cancer and heart failure clinical trials, and retrospective and prospective clinical studies, including high throughput observations.
Israel D. Sithu, PhD
Israel Sithu is a member of the research team of the Bioanalytics and Biomarker Core. He is an Assistant Professor of Physiology and Biophysics at the University of Louisville. Broadly, his research examines the molecular mechanisms of inflammatory disease process in order to inhibit progression of the disease. He has studied endothelial function and platelet activation for the last 10 years and has recently focused on examining the effect of acrolein and cigarette smoke on platelet activation and vascular dysfunction.
Sanjay Srivastava, PhD
Sanjay Srivastava is the Director of the Center’s Bioanalytical and Biomarker Core. He is Professor of Medicine and Director of the Superfund Research Center at the University of Louisville. He has spent much of his career studying the cardiovascular toxicity of aldehydes, suggesting that aldehydes generated by oxidative stress crosslink with the protein in the endoplasmic reticulum (ER). He has chaired or been a member on more than 25 NIH Study Sections, serves on the editorial board of Circulation Research and is a chartered member of Atherosclerosis and Inflammatory of the Cardiovascular System (AICS) study section at NIH.
Kandi L. Walker, PhD
Kandi Walker is a part of the research team working on the Cardiovascular Injury Due to Tobacco Use (Project 2) and the Cardiovascular effects of tobacco products in community-based cohorts (Project 3) projects. She is a Professor in the Department of Communication at the University of Louisville. For over 15 years her work has explored the intersection between health and interpersonal communication looking at how people perceive the social world surrounding health issues.
Projects and Cores
Project 1: Cardiovascular Toxicity of Tobacco Products
Successful completion of this project will lead to the development of an animal model to establish standard toxicity changes and to the discovery of novel biomarkers of cardiovascular injury that can be associated with tobacco exposure. This project will provide new information regarding the contribution of reactive aldehydes to the cardiovascular toxicity of cigarette smoke and smokeless tobacco. These findings will be useful in developing policies for regulating HPHC in smokeless tobacco, cigarettes, and emerging tobacco products.
- 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
Completion of this project will lead to the identification and validation of the novel biomarkers of endothelial injury that are associated with exposure to tobacco and tobacco constituents. From these studies, we will be able to assess which tobacco-associated biomarkers of injury reflect the extent and progression of cardiovascular disease and what magnitude of changes in these biomarkers translates into meaningful impacts on CVD outcomes.
- 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
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. Investigators 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.
Tobacco Product Evaluation and Exposure Core
The Tobacco Product Evaluation and Expose Core will provide members of AHA Tobacco Regulation and Addiction Center (A-TRAC) the research capabilities to 1) identify and evaluate tobacco product composition and constituents; 2) perform realistic tobacco product exposures in animal models such that delivery of tobacco products that replicates real world human exposures; 3) measure biomarkers of tobacco exposure and develop analytical techniques and approaches that improve our understanding of the complex relationship between markers of tobacco exposure and biomarkers of cardiovascular injury. The core will serve both the needs of center projects and be an active research core in its own right as it develops new and improved techniques that enhance the breadth and sensitivity of detection of tobacco product constituents and promotes better understanding of new and emerging tobacco products.
Cardiovascular Pathology Core
The Cardiovascular Pathology Core (Core C) will provide unified and validated measurements of several biomarkers of cardiovascular injury for Center Projects. Using state-of-the-art techniques, this core has already established Standard Operating Procedures (SOPs) for quantifying a range of biochemicals, metabolites, cytokines, and common and rare blood cells. The scope of the core services will not be limited to the requirements of these projects. It will refine ongoing areas of exploration and strive for developing novel assays to expand its repertoire.
The fertile and dynamic resources of the Core and the technical excellence of its investigators in cardiovascular pathology and toxicology will also enable other Tobacco Research Centers to interface with A-TRAC. The core will be housed in the Baxter II building in the Health Sciences Center of UofL. The core currently has state-of-the-art equipment for all its needs. Among the flowcytometers, the core has an LSR II an Accuri C6 and a MoFlo Legacy cell sorter. Other essential equipment includes a Cobas-Mira Plus chemistry analyzer, a CellDyn hematology analyzer, a Chrono-log aggregometer, a BioTek SynergyMX plate reader, and a Zeiss LSM 510 confocal microscope. Additional equipment for histology, immunohistochemistry and microscopic imaging are also available to core personnel.
Research Training and Education Core
The overall goal of our Multidisciplinary Educational Training Core in the AHA-Tobacco Regulation and Addiction Center (A-TRAC) is to develop the next generation of basic, clinical, and translational academic investigators in tobacco-related cardiovascular medicine and policy and to cross-train investigators in tobacco regulatory science.