Stem cell study determines most harmful vape liquids

The most toxic flavors: cinnamon and menthol.

Researchers at the University of Arizona College of Medicine -- Phoenix, the University of Illinois at Chicago and the Stanford Cardiovascular Institute discovered exposure to flavored e-liquids damages the endothelial cells, the thin layer of cells that line the interior surface of blood vessels and play an important role in heart and cardiovascular health.

The study, "Modeling Cardiovascular Risks of E-Cigarettes with Human-Induced Pluripotent Stem Cell-Derived Endothelial Cells," was published online May 27 in The Journal of the American College of Cardiology. According to researchers, cigarette smoking causes one of every three deaths that result from cardiovascular disease. While the detrimental effects of conventional cigarette smoking in cardiovascular disease are well-documented, there is scarce scientific evidence on the toxicity and health effects of e-cigarettes.

"Traditionally, e-cigarettes were considered a safe way to stop smoking," said Won Hee Lee, PhD, an assistant professor in the Department of Basic Medical Sciences at the UA College of Medicine -- Phoenix and co-lead and co-senior author of the study. "Our research calls that idea into question. Despite the rapid increase in popularity, the cardiovascular effects of chemical flavoring in e-cigarettes largely has been unexplored. Using a novel approach of stem cell research, we discovered the harmful effects of these flavorings and the potential cardiovascular risks users may face."

Researchers used human-induced pluripotent stem cells, derived endothelial cells (iPSC-ECs) and a screening approach to assess endothelial integrity following exposure to six different e-liquids with varying nicotine concentrations and blood collected from e-cigarette users.

Induced pluripotent stem cells (iPSC) are generated from adult cells that are reprogrammed to enable the development of an unlimited source of any type of human cell needed, which allows researchers to model diseases in a dish.

The vascular endothelium plays a key role in vascular function, which has been shown to be disrupted by cardiovascular risk factors, including cigarette smoking. After exposing these stem cells to the compounds in e-cigarettes or serum from an e-cigarette, users developed endothelial cell dysfunction associated with decreased viability, accumulation of reactive oxygen species and impaired proangiogenic properties, which is the process of creating new blood vessels. Endothelial dysfunction often precedes cardiovascular diseases. Blood serum from e-cigarette users showed harmful effects, similar to those of tobacco cigarettes on blood vessels.

"This is the first study to establish that these stem cells can reliably be used as an alternative model to research the detrimental effects of e-cigarettes with existing vascular cells," Dr. Lee said.

In recent years, vaping has grown in popularity. According to the U.S. Surgeon General, one in 20 middle school students and one in five high schoolers used e-cigarettes in 2017, a 78-percent increase from the previous year. This marks the largest increase in youth use of any substance in the 40 years the Surgeon General's office has surveyed youth drug use.

Results of the research concluded that acute exposure to flavored e-liquids or e-cigarettes worsens endothelial dysfunction, which often precedes cardiovascular diseases. The cytotoxicity, which is the ability of certain chemicals to destroy living cells, of the e-liquids varied, with cinnamon-flavored products being most potent.

Researchers believe that cinnamon and menthol vape flavorings are more toxic to the body because of the chemicals used to make those flavorings.

"There is no safe way to vape," Dr. Lee said. "It's not as safe as originally thought, especially with the flavoring. Most people expect cigarettes to be worse for our health because of the nicotine. However, that's not necessarily correct. Some of the effects of exposure to the e-liquids were dependent on the nicotine concentration but others were independent showing a combined effect of nicotine concentrations and flavoring components."

Dr. Lee said she is interested in continuing her research to see if she can apply this model to other diseases.

"Using stem cells could provide a new resource to understand the personal and the common genetic underpinnings related to the development of many related cardiovascular diseases," Dr. Lee said. "This study demonstrates and supports that human-induced pluripotent stem cells derived endothelial cells represent a robust model for investigating endothelial biology with clear advantages over primary human endothelial cells."