Abstract
Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a target for disease prevention. However, the relationship between ACE2 expression and its clinical implications in SARS-CoV-2 pathogenesis remain unknown. We demonstrated that ACE2 was predominantly overexpressed on the apical surface of bronchial epithelium, while reduced in alveolar epithelium, owing to the dramatically decreased abundance of alveolar type II pneumocytes in CS-exposed mouse lungs. Consistent with this, ACE2 was primarily significantly overexpressed in human bronchial and alveolar epithelial cells in smokers (n=99) than non-smokers (n=125), regardless of age or gender. Decreased ACE2 expression was observed in bronchial epithelial cells from ex-smokers (n=18) compared with current smokers (n=81), especially in those who had ceased smoking for more than 10 years. Moreover, ACE2 expression was positively correlated with the levels of CS-induced oxidative stress-related markers HIF-1α, iNOS, and 4-HNE in both mouse and human bronchioles. The results were further validated using a public available dataset from The Cancer Genome Atlas (TCGA) and our previous integrated data from Affymetrix U133 Plus2.0 microarray (AE-meta). Finally, our results showed that HIF-1α transcriptionally upregulates ACE2 expression. Our results indicate that smoking-induced ACE2 overexpression in the apical surface of bronchial epithelial cells provide a route by which SARS-CoV-2 enters host cells, which supports clinical relevance in attenuating the potential transmission risk of COVID-19 in smokers by smoking cessation.
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, OA2580.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021