Abstract Body (Do not enter title and authors here): Introduction: Although electronic cigarettes (e-cigs) have been known to increase the risk of vascular complications, little is known about whether e-cig represents an independent risk factor for the development and worsening of obesity and its associated vascular diseases. We hypothesize that a high-fat diet (HFD) enhances e-cig-induced vascular complications.
Methods: Male and female eight-week-old C57Bl/6J mice were fed normal chow (NC) or HFD for 15 weeks before being exposed to e-cigs (PG/VG only [PGVG] or PG/VG + 24 mg/ml nicotine [Nic]) or fresh air (FA) for 12 weeks (n=6-8). At the end of the experiments, glucose level and thoracic aortic responses to phenylephrine (PE), acetylcholine (ACh), and sodium nitroprusside (SNP) were assessed via the glucose tolerance test (GTT) and wire myography, respectively. Total RNA from male aortas was extracted and RNA-seq was utilized to identify the transcriptomic changes in our diet-induced obesity mouse model subjected to e-cig vapors (n=4).
Results: Compared to NC with FA, HFD alone caused glucose intolerance as shown by the GTT, which was improved only by exposure to nicotine-containing e-cigs (HFD+Nic). Similar improvement in glucose intolerance were found in the NC group with e-cigs (PGVG or Nic). In addition, both NC and HFD-fed male mice exhibited endothelial dysfunction characterized by a decrease in the ACh-dependent (endothelium) relaxation of PE-induced contractions. Importantly, nicotine-containing e-cig exposure (Nic) dramatically reduced the sensitivity of the aorta in the HFD group (HFD+Nic) to both ACh and SNP, while it only affected the sensitivity and maximum relaxation to ACh in the male NC group (NC+Nic). There were no significant differences in the vasoreactivity of female mice exposed to e-cig or HFD. Finally, RNA-seq results suggested that e-cig-treated male mice had altered expression of genes related to endothelial and smooth muscle function and metabolism, particularly fatty acid metabolism, which was also significant with the addition of HFD.
Conclusion: Collectively, our results suggest that acute e-cig exposure results in significant vascular dysfunction in male mice, which is worsened in HFD mice. The identification of genes dysregulated in mice exposed to e-cigs provides novel insights into vascular biology and could have a significant impact on our understanding of vascular complications associated with e-cig usage and provide insights into its contributions to obesity and diabetes.