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E-cigarette chemical effects on endothelial function

Institution: Stanford University
Investigator(s): Eric Gross, MD, PhD
Award Cycle: 2017 (Cycle 26) Grant #: 26IP-0038 Award: $380,870
Subject Area: Cardiovascular Disease
Award Type: High Impact Pilot Award

Initial Award Abstract

Electronic cigarettes (e-cigarettes) are being marketed to people as a healthy alternative to conventional cigarettes. However, there is little scientific evidence determining how the chemical components of e-cigarettes (acetaldehyde, formaldehyde, and nicotine) affect the cardiovascular system (heart and blood vessels). Here, we will determine how the chemical components of e-cigarettes affect how the cells lining blood vessels (endothelial cells) function. In addition, we will determine how e-cigarette vapors alter cardiovascular function in rodents. Further, ~560 million people in the world and ~1 million California residents cannot efficiently break down the chemicals in e-cigarettes (acetaldehyde and formaldehyde) due to a genetic variant in a mitochondrial enzyme, aldehyde dehydrogenase 2 (ALDH2). The genetic variant in ALDH2 almost exclusively exists for people of East Asian descent. Using cutting-edge techniques we developed in the laboratory, we will study how this specific ALDH2 genetic variant alters how e-cigarette chemicals affect endothelial and cardiovascular function. Importantly, our research team has several cutting-edge technologies to study the cellular effects of e-cigarettes in human cells or rodents. Since these effects are mainly occurring at the mitochondria, we developed several sensitive methods to measure how e-cigarette chemicals will affect mitochondrial function. We also have extensive experience in assessing cardiovascular function and cellular damage. We will use these techniques to examine the cardiovascular effects of e-cigarettes in human endothelial cells and rodents. Lastly, we also will test whether a drug which can increase ALDH2 activity can reverse the effects seen when cells or rodents are exposed to e-cigarette chemicals. In California, cigarette smoking attributes to ~$9.8 billion in health care costs, where a considerable portion of these costs are due to cardiovascular disease. Our proposed research will determine how e-cigarettes affect the cells lining blood vessels and cardiovascular function. These findings may be particularly important to people in California who have a genetic variant in ALDH2 which will not allow them to effectively break down components of e-cigarettes. Further, we will determine whether we have a therapeutic to treat the effects of e-cigarette chemicals on the heart and blood vessels.