Electronic cigarettes (e-cigarettes) are becoming exceptionally popular worldwide as an alternative to conventional cigarettes, both in smokers and people who have never smoked. To study the cardiac effect of e- cigarettes, I used ApoE knockout (ApoE KO) mice, the most commonly used murine model to study the cardiovascular effects of conventional cigarettes. ApoE KO miceon a western diet (WD) were exposed to saline, e-cigarettes without nicotine (e-cigarettes (0%)) and e-cigarettes with 2.4% nicotine (e-cigarettes (2.4%)) aerosol for 12 weeks. Our preliminary data shows that mice exposed to e-cigarettes (2.4%) have increased levels of serum FFA in comparison with Saline and e-cigarettes (0%). Additionally, e-cigarettes (2.4%) induce a decreased fractional shortening and increased oxidative stress in ApoE KO mice. A transcriptomic analysis of the e-cigarettes (2.4%) treated ApoE KO mice model shows a change in genes associated with metabolism and inflam m ation. Free fatty acids (FFA) are able to induce the production of mitochondrial reactive oxygen species (ROS). Oxidative stress play a major role in the inflammatory, metabolic and contractile changes of the dysfunctional heart. While there are several sources of ROS, it is generally accepted that the dysfunctional mitochondria is the major source of ROS overproduction. Mitochondrial dysfunction and reduced NAD+ levels are implicated in various metabolic and cardiovascular pathologies. NAD+ is a central metabolic co-factor by virtue of its redox capacity, and as such, regulates a wealth of metabolic transformations and ROS production. Animal models for obesity and smoking have shown decreased levels of NAD+. Nicotinamide riboside (NR), a newly identified precursor of NAD+, increases NAD+ and protects mice against mitochondrial dysfunction and HFD-induced metabolic abnormalities. In this study our specific aims are:
Aim 1 will demonstrate that e-cigarette-induced cardiac dysfunction requires lipolysis that will be blocked with lipolysis inhibitor, acipimox.
Aim 2, I will demonstrate that NR reversesthe oxidative stress, mitochondrial abnormalities, and cardiac dysfunction induced by e-cigarettes. FFA and NAD+ levels might be useful therapeutic targets to counteract the detrimental cardiac effects of e-cigarettes. Our study is likely to provide information so that regulatory agencies and the public can understand some of the detrimental effects of e-cigarettes. My immediate goal would be using training from SC2 grant and my prior experiences on basic research to become independent and competent faculty at CDU. Eventually this will help me to secure RO1, SC1 and other foundation grants to establish my own research team focusing on the metabolic effects of e-cigarettes and cardiac dysfunction. 1

Public Health Relevance

Tobacco products use is a leading cause of preventable death in the United States. In recent years, electronic cigarettes use by youth has increased at a disturbing rate. However, there is a lack of information on the cardiac effects of electronic cigarettes. I have shown that electronic cigarettes induce cardiac dysfunction in a mouse model. In this project, I am proposing experiments designed to determine the effects of NAD+ and free fatty acids levels regulation in mitochondrial dysfunction and ultimately aid in the development of effective medical therapies to prevent electronic-cigarette-induced cardiac dysfunction.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Pilot Research Project (SC2)
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Special Emphasis Panel (ZGM1)
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Beck, Lawrence A
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Charles R. Drew University of Medicine & Science
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
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