Espinoza-Derout, Jorge
Project Summary:
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.
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