Electronic cigarettes (EC) have gained significant popularity in the US since their introduction on the market eight years ago. Currently, ECs are not regulated by the FDA, partly because their effects on health have not been well characterized. Although ECs do not produce smoke and their users are not exposed to tar and carbon monoxide, they like other tobacco products deliver nicotine, which is the primary addictive component of tobacco. Nicotine has been shown to promote atherosclerosis by generating systemic oxidative stress leading to lipid peroxidation and atherosclerotic plaque formation, induce endothelial dysfunction and disrupt the integrity of vascular endothelial cells. This knowledge allows us to postulate that ECs may contribute to adverse cardiovascular health outcomes and should be regulated like traditional cigarettes (TC). Our long-term goal is to elucidate the effects of EC on vascular health, thereby providing scientific evidence for regulatory decisions contemplated by the Center for Tobacco Control. The objective of this proposal is to establish acute and chronic effects of EC use on systemic and local markers of inflammation and oxidative stress. Our central hypothesis is that EC use promotes cardiovascular disease by increasing systemic oxidative stress and endothelial toxicity. To test this hypothesis, we will pursue the following specific aims.
Aim 1 : To characterize the effects of chronic e-cigarette smoking on systemic oxidative stress. The working hypothesis for this aim is that the EC use is associated with an increase in systemic oxidative stress. To attain this Aim, we will measure the validated and sensitive markers of oxidative stress: plasma and urinary levels of F2-isoprostanes, in nonsmokers, chronic EC users, TC smokers as positive controls.
Aim 2 : To determine the acute effects of e-cigarette smoking on endothelial cell integrity. The working hypothesis for this aim is that the use of e- cigarettes leads to endothelial injury resulting in an increase in the number of endothelial progenitor cells (EPC). We will measure the levels of EPC and their colony-forming units in EC users and TC smokers immediately before and after smoking a cigarette or EC use using nonsmokers as controls.
Aim 3 : To identify the effects of chronic e-cigarette usage on endothelial function. The working hypothesis for this aim is that the EC use is linked to a reduction in eNOS activity and at the same time an increase in markers of vascular inflammation, such as NF-kB. Using a minimally-invasive technique of endothelial biopsy, we will test our hypothesis by comparing the brachial artery flow-mediated dilatation measurements and the production of NF- kB and eNOS expression by the endothelial cells harvested from the veins of EC users and control non- smoker subjects including TC smokers as positive controls. Expected outcomes will provide immediate information on the likeliest harmful effects on ECs and help guide the FDA policymaking regarding EC safety.

Public Health Relevance

There are over 6 million electronic cigarette users in the U.S., and this number is rapidly growing. Although there is vast knowledge about adverse impact of tobacco smoking on human health, the biological effects of electronic cigarettes remain largely unknown. Our proposal aims to link electronic cigarette use to several validated markers of cardiovascular disease. Establishing such a link will help inform rational policymaking and prevent renormalization of smoking behavior in the society.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Research Grants (R03)
Project #
5R03HL132570-02
Application #
9351561
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Postow, Lisa
Project Start
2016-09-30
Project End
2019-08-31
Budget Start
2017-09-01
Budget End
2019-08-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065