Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation

Hinds, D. M.; Nick, H. J.; Vallin, T. M.; Bloomquist, L. A.; Christeson, S.; Bratcher, P. E.; Cooper, E. H.; Brinton, J. T.; Bosco-Lauth, A.; White, C. W.

doi:10.1101/2022.05.20.492852

bioRxiv · 10.1101/2022.05.20.492852

Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation

Hinds, D. M.·Nick, H. J.·Vallin, T. M.·Bloomquist, L. A.·Christeson, S.·Bratcher, P. E.·Cooper, E. H.·Brinton, J. T.·Bosco-Lauth, A.·White, C. W.

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Abstract

IntroductionE-cigarette vaping has become a major portion of nicotine consumption, especially for children and young adults. Although it is branded as a safer alternative to cigarette smoking, murine and rat models of sub-acute and chronic e-cigarette vaping exposure have shown many pro-inflammatory changes in the respiratory tract. An acute vaping exposure paradigm has not been demonstrated in the golden Syrian hamster, and the hamster is a readily available small animal model that has the unique benefit of becoming infected with and transmitting SARS-CoV-2 without genetic alteration to the animal or virus. MethodsUsing a two-day, whole-body vaping exposure protocol in male golden Syrian hamsters, we evaluated serum cotinine, bronchoalveolar lavage cells, lung and nasal histopathology, and gene expression in the nasopharynx and lung through RT-qPCR. Depending on the presence of nonnormality or outliers, statistical analysis was performed by ANOVA or Kruskal-Wallis tests. For tests that were statistically significant (p-value <0.05), post-hoc Tukey-Kramer and Dunns tests, respectively, were performed to make pairwise comparisons between groups. ResultsIn nasal tissue, RT-qPCR analysis revealed nicotine-dependent increases in genes associated with type 1 inflammation (CCL-5 and CXCL-10), fibrosis (TGF-{beta}), and a nicotine-independent decrease in the vasculogenesis/angiogenesis gene VEGF-A. In the lung, nicotine-dependent increases in the expression of genes involved in the renin-angiotensin pathway (ACE, ACE2), coagulation (tissue factor, Serpine-1), extracellular matrix remodeling (MMP-2, MMP-9), type 1 inflammation (IL-1{beta}, TNF-, and CXCL-10), fibrosis (TGF-{beta} and Serpine-1), oxidative stress response (SOD-2), neutrophil extracellular traps release (ELANE), and vasculogenesis and angiogenesis (VEGF-A) were identified. ConclusionTo our knowledge, this is the first demonstration that the Syrian hamster is a viable model of e-cig induced inhalational injury. In addition, this is the first report that e-cig vaping with nicotine can increase tissue factor gene expression in the lung. Our results show that even an acute exposure to e-cigarette vaping causes significant upregulation in the respiratory tract of pathways involving the renin-angiotensin system, coagulation, extracellular matrix remodeling, type 1 inflammation, fibrosis, oxidative stress response, NETosis, vasculogenesis, and angiogenesis.

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Hinds, D. M., Nick, H. J., Vallin, T. M., Bloomquist, L. A., Christeson, S., Bratcher, P. E., Cooper, E. H., Brinton, J. T., Bosco-Lauth, A., White, C. W.. 2022-05-21. Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation. https://doi.org/10.1101/2022.05.20.492852

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