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Effect of age on human ACE2 and ACE2-expressing alveolar type II cells levels

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19. Viral entry requires ACE2 and transmembrane protease serine 2 (TMPRSS2). Transcriptomic studies showed that children display lower ACE2 than adul...

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Autores principales: Silva, Mauro G., Falcoff, Nora L., Corradi, Gerardo R., Di Camillo, Norma, Seguel, Rolando F., Tabaj, Gabriela C., Guman, Gabriela R., de Matteo, Elena, Nuñez, Myriam, Gironacci, Mariela M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219367/
https://www.ncbi.nlm.nih.gov/pubmed/35739259
http://dx.doi.org/10.1038/s41390-022-02163-z
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author Silva, Mauro G.
Falcoff, Nora L.
Corradi, Gerardo R.
Di Camillo, Norma
Seguel, Rolando F.
Tabaj, Gabriela C.
Guman, Gabriela R.
de Matteo, Elena
Nuñez, Myriam
Gironacci, Mariela M.
author_facet Silva, Mauro G.
Falcoff, Nora L.
Corradi, Gerardo R.
Di Camillo, Norma
Seguel, Rolando F.
Tabaj, Gabriela C.
Guman, Gabriela R.
de Matteo, Elena
Nuñez, Myriam
Gironacci, Mariela M.
author_sort Silva, Mauro G.
collection PubMed
description BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19. Viral entry requires ACE2 and transmembrane protease serine 2 (TMPRSS2). Transcriptomic studies showed that children display lower ACE2 than adults, though gene expression levels do not always correlate with protein levels. We investigated the effect of age on ACE2 and TMPRSS2 protein expression in alveolar type II (AT2) cells in the lungs of children compared to adults. We also analysed the ratio of Ang-(1–7) to Ang II as a surrogate marker of ACE2 activity in the subjects’ lung parenchyma. METHODS: Ang II and Ang-(1–7) levels and ACE2 and TMPRSS2 protein expression were measured by radioimmunoassay and immunohistochemistry, respectively. RESULTS: The amount of ACE2-expressing AT2 cells and ACE2 protein content were lower in children than in adults. Ang II levels were higher in children compared to adults and inversely correlated with the amount of ACE2-expressing AT2 cells. Children presented lower Ang-(1–7)/Ang II ratio than adult suggesting lower ACE2 activity in children. TMPRSS2 protein expression was not influenced by age. CONCLUSIONS: These results expand on previous transcriptomic studies and may partially explain the low susceptibility of children to SARS-CoV-2 infection. CATEGORY OF STUDY: Clinical original research IMPACT: Children display lower ACE2 protein content and activity compared to adults. Ang II levels were higher in children compared to adults and inversely correlated with the amount of ACE2-expressing AT2 cells. TMPRSS2 protein expression was not influenced by age. These results expand on previous transcriptomic studies and may partially explain the low susceptibility of children to SARS-CoV-2 infection.
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spelling pubmed-92193672022-06-23 Effect of age on human ACE2 and ACE2-expressing alveolar type II cells levels Silva, Mauro G. Falcoff, Nora L. Corradi, Gerardo R. Di Camillo, Norma Seguel, Rolando F. Tabaj, Gabriela C. Guman, Gabriela R. de Matteo, Elena Nuñez, Myriam Gironacci, Mariela M. Pediatr Res Clinical Research Article BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19. Viral entry requires ACE2 and transmembrane protease serine 2 (TMPRSS2). Transcriptomic studies showed that children display lower ACE2 than adults, though gene expression levels do not always correlate with protein levels. We investigated the effect of age on ACE2 and TMPRSS2 protein expression in alveolar type II (AT2) cells in the lungs of children compared to adults. We also analysed the ratio of Ang-(1–7) to Ang II as a surrogate marker of ACE2 activity in the subjects’ lung parenchyma. METHODS: Ang II and Ang-(1–7) levels and ACE2 and TMPRSS2 protein expression were measured by radioimmunoassay and immunohistochemistry, respectively. RESULTS: The amount of ACE2-expressing AT2 cells and ACE2 protein content were lower in children than in adults. Ang II levels were higher in children compared to adults and inversely correlated with the amount of ACE2-expressing AT2 cells. Children presented lower Ang-(1–7)/Ang II ratio than adult suggesting lower ACE2 activity in children. TMPRSS2 protein expression was not influenced by age. CONCLUSIONS: These results expand on previous transcriptomic studies and may partially explain the low susceptibility of children to SARS-CoV-2 infection. CATEGORY OF STUDY: Clinical original research IMPACT: Children display lower ACE2 protein content and activity compared to adults. Ang II levels were higher in children compared to adults and inversely correlated with the amount of ACE2-expressing AT2 cells. TMPRSS2 protein expression was not influenced by age. These results expand on previous transcriptomic studies and may partially explain the low susceptibility of children to SARS-CoV-2 infection. Nature Publishing Group US 2022-06-23 2023 /pmc/articles/PMC9219367/ /pubmed/35739259 http://dx.doi.org/10.1038/s41390-022-02163-z Text en © The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc 2022 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Clinical Research Article
Silva, Mauro G.
Falcoff, Nora L.
Corradi, Gerardo R.
Di Camillo, Norma
Seguel, Rolando F.
Tabaj, Gabriela C.
Guman, Gabriela R.
de Matteo, Elena
Nuñez, Myriam
Gironacci, Mariela M.
Effect of age on human ACE2 and ACE2-expressing alveolar type II cells levels
title Effect of age on human ACE2 and ACE2-expressing alveolar type II cells levels
title_full Effect of age on human ACE2 and ACE2-expressing alveolar type II cells levels
title_fullStr Effect of age on human ACE2 and ACE2-expressing alveolar type II cells levels
title_full_unstemmed Effect of age on human ACE2 and ACE2-expressing alveolar type II cells levels
title_short Effect of age on human ACE2 and ACE2-expressing alveolar type II cells levels
title_sort effect of age on human ace2 and ace2-expressing alveolar type ii cells levels
topic Clinical Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219367/
https://www.ncbi.nlm.nih.gov/pubmed/35739259
http://dx.doi.org/10.1038/s41390-022-02163-z
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