E-cigarettes confer endothelial dysfunction similar to traditional cigarettes
Click Here to Manage Email Alerts
Reduced flow-mediated dilation was observed among both e-cigarette and traditional cigarette users, but circulating levels of certain inflammatory and thrombotic mediators differed between the two groups, researchers reported.
Researchers wrote that endothelial dysfunction associated with e-cigarettes and traditional cigarettes as well as differing patterns in CVD biomarkers observed between the two may be indicative of significant vascular risk among dual users of both e-cigarettes and traditional cigarettes, according to data published in Arteriosclerosis, Thrombosis, and Vascular Biology.
“Our findings offer important insight about a timely and much debated issue of public health and regulatory policy: whether incomplete switching from smoking to e-cigarette use (resulting in dual product use) leads to reduced harm. This is a common assumption by the public, and this assumption is present in the FDA Marketing Granted Orders for RJ Reynolds’ Vuse, Logic, and NJOY e-cigarette and heated tobacco products,” Leila Mohammadi, MD, PhD, assistant researcher at UCSF School of Medicine, and colleagues wrote. “We found that chronic e-cigarette use and smoking resulted in comparable impairment of vascular endothelial function and in altered serum that blunted nitric oxide production from endothelial cells. However, the distinct patterns of circulating CVD risk biomarkers from chronic users of each product indicate that despite the similar physiological effects, e-cigarette use and smoking trigger fundamentally different molecular responses. These differences indicate that at least for vascular health, dual product use may not result in reduced harm, and may actually be worse.”
Flow-mediated dilation is caused by the release of nitric oxide by endothelial cells, according to a study in the American Journal of Physiology, and endothelial dysfunction is an early indicator of CVD, according to the present study. Therefore, researchers measured brachial artery flow-mediated dilation to access the effects of chronic e-cigarette use on endothelial function.
For this study, 120 participants were recruited at University of California, San Francisco, Boston University Medical School and the University of Louisville, and blood was collected by venipuncture with participants in a fasting state. Measure of flow-mediated dilation were available in 51 participants. Participants were identified as chronic e-cigarette users, chronic cigarette smokers and nonusers; all users of either e-cigarettes or regular cigarettes used one or the other, not both.
Mechanisms behind e-cigarette-related endothelial dysfunction
Researchers observed higher mean brachial artery flow-mediated dilation among nonusers compared with chronic users of e-cigarettes (10.7% vs. 5.3%; P < .001) and those who smoke cigarettes (10.7% vs. 6.5%; P = .014).
Serum from e-cigarette users and smokers was associated with reduced vascular endothelial growth factor-induced nitric oxide secretion among the cultured endothelial cells compared with serum from nonusers, with no reduction in endothelial nitric oxide synthase messenger RNA or protein levels, according to the study.
Nitric oxide secretion did not change in cultured endothelial cells exposed to condensed e-cigarette aerosol. The researchers posited that inhibition associated with e-cigarette use was associated with inhalation rather than directly from the aerosol.
E-cigarette user serum was also associated with increased endothelial release of H2O2 and more permeability compared with serum from nonusers.
Researchers also observed that serum from e-cigarette users had higher concentrations of the receptor for advanced glycation end products ligands S100A8 and HMGB1 compared with that from smokers and nonusers.
Moreover, endothelial permeability was reduced by receptor for advanced glycation end product inhibition among e-cigarette users — an observation not seen among smokers — and did not affect nitric oxide production.
“We observed that chronic e-cigarette use also alters the expression profile of relevant proteins, but with relatively little overlap with those increased by smoking. This is consistent with the growing awareness that vaping and smoking involve overlapping potential health risks such that dual use may be more risky than either smoking or vaping alone,” the researchers wrote. “These findings suggest a potential link between vaping and disruptions in the control of what can cross from the airways into the lung capillary bed.”
‘Novel pathway’ differentiates e-cigarette use
In a related editorial, Daniel J. Conklin, PhD, professor of medicine and core director of animal models and phenotyping at the University of Kentucky in Louisville, discussed mechanistic insights into e-cigarette-related endothelial dysfunction outlined in this study, as well as the direction of future trials.
“The authors found a novel pathway in e-cigarette users, but absent in smokers, wherein elevated S100A8 and HMGB1 increase endothelial cell permeability via receptor of advanced glycation end products. This is a unique observation that surprisingly differentiates the mechanism of endothelial dysfunction of chronic e-cigarette use from use of combustible cigarettes,” Conklin wrote. “However, the degree of flow-mediated dilation impairment is not highly correlated with per person sera nitric oxide inhibition, and although vexing, it remains to be seen whether circulating factors result from acute stimulation of the nervous system or as a distinct secondary result of chronic use. Perhaps, in a trial where chronic e-cigarette users either receive a receptor of advanced glycation end products inhibitor or abstain from use would allow for temporal assessment of the reversibility of flow-mediated dilation impairment and sera-induced endothelial cell toxicity, and thus, potentially reveal their interdependence.”
References:
- Conklin DJ. Arterioscler Thromb Vasc Biol. 2022;doi:10.1161/ATVBAHA.122.318468.
- Kelm M, et al. Am J Physiol Heart Circ Physiol. 2002;doi:10.1152/ajpheart.2002.282.1.H1.
Collapse
Click Here to Manage Email Alerts