Background: The harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial func­tion are less understood. We hypothesized that e-cigarette use causes changes in blood milieu that impair endothelial function. 

Methods: Endothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers. We measured the effects of participants’ sera, or e-cigarette aerosol condensate, on nitric oxide (NO) and H₂O₂ release and cell permeability in culture endothelial cells (ECs). 

Results: E-cigarette users and smokers had lower FMD than nonusers. Sera from e-cigarette users and smokers reduced VEGF-induced NO secretion by ECs relative to nonuser sera, without significant reduction in endothelial NO synthase mRNA or protein levels. E-cigarette user sera, but not smoker sera, caused increased endothelial release of H₂O₂, and more permeability, than nonuser sera. E-cigarette users and smokers exhibited changes in circulating biomarkers of inflammation, thrombosis, and cell adhesion relative to nonusers, but with distinct profiles. E-cigarette user sera had higher concentrations of the RAGE ligands S100A8 and HMGB1 than smoker and nonuser sera, and RAGE inhibition reduced permeability induced by e-cigarette user sera but did not affect NO production. 

Conclusion: Chronic vaping and smoking both impair FMD and cause changes in the blood that inhibit endothelial NO release. Vaping, but not smoking, causes changes in the blood that increase microvascular endothelial permeability and may have a vaping-specific effect on intracellular oxidative state. Our results suggest a role for RAGE in e-cigarette-induced changes in endothelial function. 

FMD measurement: High-resolution ultrasound of the right brachial artery was performed one cm distal to the antecubital fossa with a 10 MHz linear array probe coupled to a GE Vivid 7 Imaging System and Sonosite M-turbo. Digital images for FMD were analyzed with dedicated software (Information Integrity Inc.; Iowa City, Iowa).

Generation of e-cigarette aerosol and its condensates: A Gram Universal Vaping Machine (Gram Research, Oakland, CA) was used to generate aerosol.

Measurement of NO production: The amount of NO released by the cells was measured by the chemilumin­escence method using an NO analyzer (model 280i, GE/Zysense, Weddington, NC)

Measurement of relative expression of NOS3 gene: qPCR was conducted using TaqMan^TM Gene Expression Master Mix with NOS3 TaqMan^TM FAM-MGB Probes in a ViiA7 Real-Time PCR system (Applied Biosystems). 

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