Feature

Q&A: E-cigarette flavoring detrimental to endothelial cell function

Won Hee Lee
Won Hee Lee

Increased exposure to flavored liquids used in electronic cigarettes, most notably cinnamon, worsens endothelial dysfunction and can be a precursor to CVD.

This finding, which Won Hee Lee, PhD, and colleagues published in the Journal of the American College of Cardiology, was the first proof-of-principle study looking at how induced pluripotent stem cells are affected by flavored e-cigarette liquids.

Lee, an assistant professor in the department of basic medical sciences at the University of Arizona College of Medicine and an instructor at the Stanford Cardiovascular Institute at the Stanford University School of Medicine, and colleagues recruited nonsmokers, active cigarette smokers, active dual-use cigarette/e-cigarette smokers and active e-cigarette users (mean age, 29 years) who were healthy and free from CV risk factors.

Lee spoke with Cardiology Today about the impact of the study and the potential for future investigation.

Question: What led to you and your group undertaking the study?

Answer: The use of e-cigarettes has increased dramatically since their introduction a decade ago. Notably, an explosive increase in the use of e-cigarettes among middle and high school students is happening with scarce scientific evidence on their health effects. As stem cell researchers in the field of CV research, we were interested to evaluate if stem cells and its derivatives can be used to understand the potential adverse effects of e-cigarette use on CV health.

Increased exposure to flavored liquids used in electronic cigarettes, most notably cinnamon, worsens endothelial dysfunction and can be a precursor to CVD.
Source: Adobe Stock

Q: What do these findings add to the knowledge base?

A: To our knowledge, our study is the first proof-of-principle study to establish that human-induced pluripotent stem cell-derived endothelial cells can be reliably used as an alternative model to current existing vascular cells for studying the detrimental effects of e-cigarettes. We believe our study is also among the first to reveal novel mechanistic insights looking at the crosstalk between e-cigarettes and macrophages that might be linked to e-cigarette-induced reactive oxygen species generation molecules that can cause DNA damage and endothelial dysfunction, which is an important risk factor for the development of CVD.

Q: What implications do the findings have for clinical practice?

A: Growing evidence is accruing that shows e-cigarette use has serious detrimental effects on CV health. As e-cigarettes are one of the most controversial issues in public health today and epidemiological evidence of long-term health effects of e-cigarette on CV outcomes is currently unavailable, it is reasonable to communicate to smokers the relative risks of tobacco smoking and e-cigarette vaping based on current knowledge, keeping in mind that the ideal pathway is to quit without using any alternative product.

Q: What makes the cinnamon-flavored e-cigarette liquid the most potent compared with other flavors?

A: E-cigarette liquid contains various chemical substances that are known to be toxic to human cells and these refill e-liquids vary significantly from product to product. According to previous studies on analyzing chemicals in the cinnamon-flavored refill fluids, four chemicals — cinnamaldehyde (CAD), 2-methoxycinnamaldehyde (2MOCA), dipropylene glycol and vanillin — were identified in the refill fluids, and CAD and 2MOCA showed high cytotoxicity to the cells (Bahl V, et al. Reprod Toxicol. 2012;doi:10.1016/j.reprotox.2012.08.001 and Behar RZ, et al. Tob Control. 2016;doi:10.1136/tobaccocontrol-2016-053224). Although most of the flavoring chemicals in e-liquids may meet the generally recognized safe standard for ingestion as food additives, that does not mean they are safe to inhale as inhalants.

Q: What are the most important take-home messages from this study?

A: I would say do not use e-cigarettes with the assumption that switching to e-cigarettes will be good for CV health. Contrary to what people think, e-cigarettes are not perfectly safe.

Q: What are avenues for future research and beyond?

A: [Induced pluripotent stem cells] 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. We are interested in looking at the health effects on the heart and the brain. - by Earl Holland Jr.

Reference:

Lee WH, et al. J Am Coll Cardiol. 2019;doi:10.1016/j.jacc.2019.03.476.

For more information:

Won Hee Lee, PhD, can be reached at 425 N. Fifth St., Room 426, Phoenix, AZ 85004-2157; email: whlee@email.arizona.edu.

Disclosure: Lee reports no relevant financial disclosures.

Won Hee Lee
Won Hee Lee

Increased exposure to flavored liquids used in electronic cigarettes, most notably cinnamon, worsens endothelial dysfunction and can be a precursor to CVD.

This finding, which Won Hee Lee, PhD, and colleagues published in the Journal of the American College of Cardiology, was the first proof-of-principle study looking at how induced pluripotent stem cells are affected by flavored e-cigarette liquids.

Lee, an assistant professor in the department of basic medical sciences at the University of Arizona College of Medicine and an instructor at the Stanford Cardiovascular Institute at the Stanford University School of Medicine, and colleagues recruited nonsmokers, active cigarette smokers, active dual-use cigarette/e-cigarette smokers and active e-cigarette users (mean age, 29 years) who were healthy and free from CV risk factors.

Lee spoke with Cardiology Today about the impact of the study and the potential for future investigation.

Question: What led to you and your group undertaking the study?

Answer: The use of e-cigarettes has increased dramatically since their introduction a decade ago. Notably, an explosive increase in the use of e-cigarettes among middle and high school students is happening with scarce scientific evidence on their health effects. As stem cell researchers in the field of CV research, we were interested to evaluate if stem cells and its derivatives can be used to understand the potential adverse effects of e-cigarette use on CV health.

Increased exposure to flavored liquids used in electronic cigarettes, most notably cinnamon, worsens endothelial dysfunction and can be a precursor to CVD.
Source: Adobe Stock

Q: What do these findings add to the knowledge base?

A: To our knowledge, our study is the first proof-of-principle study to establish that human-induced pluripotent stem cell-derived endothelial cells can be reliably used as an alternative model to current existing vascular cells for studying the detrimental effects of e-cigarettes. We believe our study is also among the first to reveal novel mechanistic insights looking at the crosstalk between e-cigarettes and macrophages that might be linked to e-cigarette-induced reactive oxygen species generation molecules that can cause DNA damage and endothelial dysfunction, which is an important risk factor for the development of CVD.

Q: What implications do the findings have for clinical practice?

A: Growing evidence is accruing that shows e-cigarette use has serious detrimental effects on CV health. As e-cigarettes are one of the most controversial issues in public health today and epidemiological evidence of long-term health effects of e-cigarette on CV outcomes is currently unavailable, it is reasonable to communicate to smokers the relative risks of tobacco smoking and e-cigarette vaping based on current knowledge, keeping in mind that the ideal pathway is to quit without using any alternative product.

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Q: What makes the cinnamon-flavored e-cigarette liquid the most potent compared with other flavors?

A: E-cigarette liquid contains various chemical substances that are known to be toxic to human cells and these refill e-liquids vary significantly from product to product. According to previous studies on analyzing chemicals in the cinnamon-flavored refill fluids, four chemicals — cinnamaldehyde (CAD), 2-methoxycinnamaldehyde (2MOCA), dipropylene glycol and vanillin — were identified in the refill fluids, and CAD and 2MOCA showed high cytotoxicity to the cells (Bahl V, et al. Reprod Toxicol. 2012;doi:10.1016/j.reprotox.2012.08.001 and Behar RZ, et al. Tob Control. 2016;doi:10.1136/tobaccocontrol-2016-053224). Although most of the flavoring chemicals in e-liquids may meet the generally recognized safe standard for ingestion as food additives, that does not mean they are safe to inhale as inhalants.

Q: What are the most important take-home messages from this study?

A: I would say do not use e-cigarettes with the assumption that switching to e-cigarettes will be good for CV health. Contrary to what people think, e-cigarettes are not perfectly safe.

Q: What are avenues for future research and beyond?

A: [Induced pluripotent stem cells] 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. We are interested in looking at the health effects on the heart and the brain. - by Earl Holland Jr.

Reference:

Lee WH, et al. J Am Coll Cardiol. 2019;doi:10.1016/j.jacc.2019.03.476.

For more information:

Won Hee Lee, PhD, can be reached at 425 N. Fifth St., Room 426, Phoenix, AZ 85004-2157; email: whlee@email.arizona.edu.

Disclosure: Lee reports no relevant financial disclosures.