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Human iPSCs for Elucidating Cardiovascular Risks of E-Cigare

Institution: Stanford University
Investigator(s): Joseph Wu, M.D., Ph.D.
Award Cycle: 2018 (Cycle 27) Grant #: 27IR-0012 Award: $1,177,500
Subject Area: Cardiovascular and Cerebrovascular Disease
Award Type: High Impact Research Project Award
Abstracts

Initial Award Abstract

Cigarette smoking remains the leading cause of preventable death in the United States, responsible for approximately half a million deaths per year. Evidence has shown that smoking can harm nearly all organs of the body, with the greatest morbidity and mortality in the lung and heart.  In recent years, electronic cigarettes (e-cigarettes) have risen in popularity to become the top smoking cessation aid. E-cigarettes are devices designed to imitate regular cigarettes that deliver a nicotine-containing aerosol to users by heating a solution typically consisting of propylene glycol or glycerol (glycerin), nicotine, and flavoring agents via inhalation without combusting tobacco. Although e-cigarettes are marketed as a safer alternative to conventional cigarettes, their use is not without controversy, and the scientific community has been concerned because the potential harmful health effects of e-cigarette smoking are largely unknown. Unanswered questions remain about their overall toxicological effects and safety, efficacy of harm reduction, and mechanism(s) of action. In addition, e-cigarette smoking’s effects on the cardiovascular function remain poorly understood. Smokers develop various forms of smoking-related cardiovascular disease with a diverse severity and speed of progress suggesting that individual genetic factors play a key role in the development of cardiovascular disease. However, it is difficult to prove currently due to the lack of an appropriate human model.  

With the advent of patient-specific induced pluripotent stem cells (iPSCs) that can be differentiated into disease-relevant cell types, such as heart cells and endothelial cells, investigation of e-cigarette smoking-related cardiovascular dysfunction with unique human genetic background becomes feasible. The key objective of this TRDRP High Impact Research Project Award proposal is to elucidate the genetic impact on the initiation and development of e-cigarette smoking-related cardiac and endothelial dysfunction at the cellular level. Data collected using this methodology can inform the public about the potential deleterious consequences of e-cigarette smoking and second-hand exposure to e-cigarettes. The proposed studies would give the FDA important knowledge-based tools to protect the public health in today’s rapidly evolving tobacco marketplace, including the review of new e-cigarette products and their health-related claims.