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Using a new culture system, the researchers found that endothelial stem cells exposed to electronic cigarette flavored liquids exhibited decreased cell viability and function.
When exposed to several different e-liquids, endothelial cells derived from stem cells exhibited increased levels of reactive oxygen species (ROS), inflammatory signaling, and lipoprotein uptake. low density, as well as an alteration of the formation and migration of the tubes.
"Often, patients say:" Hey doc, I'm trying to quit, can I switch to e-cigarettes because they're safer for me? & # 39; "Said Joseph C. Wu, MD, PhD, Stanford School of Medicine, California, in an interview.
"But the reality is that, besides nicotine, which has adverse cardiovascular effects, electronic cigarettes – even when liquids do not contain nicotine – have other flavoring components that can cause vascular dysfunction, particularly inflammation, apoptosis and cell death, and the activation of oxidative stress.I therefore think that the best advice that one can give to a patient as a doctor is to quit, rather than switch to e-cigarettes. "
The findings of the Wu team, led by first author Won Lee Hee, PhD, a former Stanford Fellow who is now at the University of Arizona, Phoenix, have been published in the June 4th issue of Journal of the American College of Cardiology.
Wu acknowledged that although some patients manage to quit smoking by opting for the electronic cigarette, many others fail to do so, and the use of e-cigarettes by teens is alarming.
"More and more teenagers are smoking electronic cigarettes because they think it's safer than regular cigarettes, which is true from a carcinogenic point of view, but there are still some problems, for example for cardiovascular health.I think for society as a whole, this could lead to far greater damage in the long run than we realize if we had a whole generation of adolescents who were addictive to the electronic cigarette, "said Wu.
To test the impact of e-liquids – the "juice" used in an e-cigarette – on endothelial integrity, the researchers used endothelial cells derived from induced pluripotent stem cells (iPSC-EC) from of three healthy volunteers and one population of subjects. this included five healthy non-smokers, five active smokers, two dual-use users of electronic cigarettes and cigarettes, and two users of electronic cigarettes only.
High throughput screening was used to study the effects of e-liquids on endothelial cell viability by treating iPSC-EC with a dilution of six different e-liquids with varying nicotine concentrations, including some without nicotine. .
The six flavored electronic liquids tested had adverse effects on endothelial cell function, but a cinnamon flavored liquid appeared to have the worst impact, followed by a menthol flavored product.
The other flavors tested – a fruit-flavored liquid, a sweet tobacco with caramel and vanilla tones, a tobacco flavored product and a butterscotch liquid – all had moderate toxic effects on the endothelial cells.
Although most of the chemicals used in e-liquids are generally recognized as safe food additives for ingestion, they have not been sufficiently tested as 'food'. inhalants.
The researchers also performed iPSC-EC cell incubation tests with serum from non-smokers, users of electronic cigarettes, and cigarette smokers to mimic the exposure. cell in vivo.
After exposure of iPSC-EC to serum, an increase in ROS related to endothelial dysfunction was noted in the serum of smokers and smokers (relative to the serum of non-smokers), as well as an increase in Expression of cytokines. The impact on endothelial function was similar among smokers and electronic smokers.
"In these tests, we validated our results and conclusively demonstrated that after the exposure of these iPSC-EC serum to electronic cigarette users, multiple inflammatory pathways were activated," said Wu.
This new study is fueling the controversy surrounding electronic cigarettes, which have grown in popularity despite the health concerns they have. What is most disturbing is the evidence of a spectacular consumption of young non-smoking cigarettes.
In adults, it appears that current smokers or quitters use e-cigarettes more often than non-smokers.
A sophisticated model, but still a model
Wu, who directs the Stanford Cardiovascular Institute and directs the laboratory in which the concept of "clinical trial in a dish" was developed, explained that it would be useful to conduct a study showing the effect electronic cigarettes on human blood vessels "we would have to strip an artery, probably from the forearm or leg, which most people would not be willing to accept."
"But with this technique, we can non-invasively extract some blood cells from patients, convert them into iPSC cells, and then generate large amounts of these vascular endothelial cells so that we can quickly study the whole process," he explained.
In an editorial commentary, Jane E. Freedman, MD, and Chinmay M. Trivedi, MD, Ph.D., both of the University of Mbadachusetts Medical School in Worchester, stated that use of CEI-CPS is "remarkable" in that these cells are derived. to reprogram adult somatic cells in pluripotency and have an "unlimited proliferation capacity".
They add, however, that the use of an in vitro culture system is "an obvious limitation" of the study, although the results are consistent with the growing evidence suggesting potential adverse effects of the use of the electronic cigarette.
For Peter Hajek, PhD, a recognized expert in the treatment of smoking cessation, the use of an in vitro model is an important limitation.
"I'm not sure what one can learn by exposing cells to an e-liquid (vapers do not pour e-liquid on their endothelial cells), especially when it's not in the body. there was no possible comparison with the effects of smoking, "he said. theheart.org | Medscape Cardiology.
"Studies that rule out smoking control will probably not provide much useful information," he added.
Hajek is director of the tobacco addiction research unit of the Wolfson Institute of Preventive Medicine at Queen Mary University in London. His group published a randomized trial in the New England Journal of Medicine a few months ago, showing that e-cigarettes were almost twice as effective as nicotine replacement products at stopping smoking at 1 year.
This work was funded by the Scientific Development Grant from the American Heart Association (AHA), a grant from the Stanford Diabetes Research Center, funded by a grant sponsored by the National Institutes of Health (NIH), and other grants awarded to various co-authors of NIH, the University. the California Tobacco Disease Research Program and the US Center for Tobacco Control for Food and Drugs. Wu said he is a co-founder of Khloris Biosciences, "but has no interest in competition, the work presented here being totally independent." Freedman and Trivedi have not reported any conflicts of interest.
J Am Coll Cardiol. 2019; 73: 2722-2737, 2738-2739. Abstract, Editorial
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