Dissecting Cardiovascular Effects of E-Cigarettes

First-hand and second-hand smoking are among the top 10 causes for global disability worldwide. A new source of emissions, the electronic cigarettes (EC), has been introduced in the last few years and is rapidly gaining strength, due to the assumption that these emissions are harmless. We have found that human subjects with chronic EC use exhibit increased oxidative stress in the blood and perturbed cardiac autonomic tone resulting in decreased heart rate variability (HRV), a marker indicative of increased cardiovascular (CV) risk. However, the mechanisms by which EC exert these actions are unknown, and there are no reports of animal models of EC exposure that resemble these CV effects. In this project, we will test our hypothesis that EC induce effects on HRV and atherosclerosis by promoting systemic oxidative stress. We will set up a mouse model exposure system that enables us to study the toxicology and mechanisms of CV effects induced by EC. With this exposure model, not only we will be able to expand our findings obtained with human studies but it will allow us to determine things that cannot or will be very difficult to study in humans. We will use mice with normal blood levels of lipids and mice that are genetically manipulated to have increased lipids in the blood to study EC effects on HRV, oxidative stress, and atherosclerosis. We will also use other type of genetically-manipulated mice to determine if increased protection against oxidative stress ameliorate effects induced by EC use. This will allow us to gain insights into factors responsible for individual susceptibility to EC-induced CV toxicity.