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ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma

Wark, PAB, Pathinayake, PS, Kaiko, G, Nichol, K, Ali, A, Chen, L, Sutanto, EN, Garratt, LW, Sohal, SS ORCID: 0000-0001-9627-6498, Lu, W, Eapen, MS ORCID: 0000-0003-0570-7059, Oldmeadow, C, Bartlett, N, Reid, A, Veerati, P, Hsu, ACY, Looi, K, Iosifidis, T, Stick, SM, Hansbro, PM and Kicic, A 2021 , 'ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma' , Respirology, vol. 26, no. 5 , pp. 442-451 , doi: 10.1111/resp.14003.

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Abstract

Background and objective: COVID-19 is complicatedby acute lung injury, and death in some individuals. Itis caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determinedwhat factors are associated with ACE2 expression particularly in patients with asthma and COPD.Methods: We obtained lower AEC from 145 people fromtwo independent cohorts, aged 2–89 years, Newcastle(n = 115) and Perth (n = 30), Australia. The Newcastlecohort was enriched with people with asthma (n= 37)and COPD (n = 38). Gene expression for ACE2 andother genes potentially associated with SARS-CoV-2 cellentry was assessed by qPCR, and protein expression wasconfirmed with immunohistochemistry on endobronchialbiopsies and cultured AEC.Results: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03),but not with pack-years smoked. When we comparedgene expression between adults with asthma, COPD andhealthy controls, mean ACE2 expression was lower inasthma patients (P = 0.01). Gene expression of furin, aprotease that facilitates viral endocytosis, was also lowerin patients with asthma (P = 0.02), while ADAM-17, adisintegrin that cleaves ACE2 from the surface, wasincreased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthmapatients.Conclusion: Increased ACE2 expression occurs in olderpeople and males. Asthma patients have reducedexpression. Altered ACE2 expression in the lower airwaymay be an important factor in virus tropism and may inpart explain susceptibility factors and why asthmapatients are not over-represented in those with COVID19 complications.

Item Type: Article
Authors/Creators:Wark, PAB and Pathinayake, PS and Kaiko, G and Nichol, K and Ali, A and Chen, L and Sutanto, EN and Garratt, LW and Sohal, SS and Lu, W and Eapen, MS and Oldmeadow, C and Bartlett, N and Reid, A and Veerati, P and Hsu, ACY and Looi, K and Iosifidis, T and Stick, SM and Hansbro, PM and Kicic, A
Keywords: asthma, ACE2, SARS-CoV-2, COVID-19, viral respiratory infections, COPD
Journal or Publication Title: Respirology
Publisher: Blackwell Publishing Asia
ISSN: 1323-7799
DOI / ID Number: 10.1111/resp.14003
Copyright Information:

© 2021 Asian Pacific Society of Respirology

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