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Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation
Mortality due to Covid-19 is highly associated with advanced age, owing in large part to severe lower respiratory tract infection. SARS-CoV-2 utilizes the host ACE2 receptor for infection. Whether ACE2 abundance in the lung contributes to age-associated vulnerability is currently unknown. We set out...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886150/ https://www.ncbi.nlm.nih.gov/pubmed/33592054 http://dx.doi.org/10.1371/journal.pone.0247060 |
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author | Baker, Steven Andrew Kwok, Shirley Berry, Gerald J. Montine, Thomas J. |
author_facet | Baker, Steven Andrew Kwok, Shirley Berry, Gerald J. Montine, Thomas J. |
author_sort | Baker, Steven Andrew |
collection | PubMed |
description | Mortality due to Covid-19 is highly associated with advanced age, owing in large part to severe lower respiratory tract infection. SARS-CoV-2 utilizes the host ACE2 receptor for infection. Whether ACE2 abundance in the lung contributes to age-associated vulnerability is currently unknown. We set out to characterize the RNA and protein expression profiles of ACE2 in aging human lung in the context of phenotypic parameters likely to affect lung physiology. Examining publicly available RNA sequencing data, we discovered that mechanical ventilation is a critical variable affecting lung ACE2 levels. Therefore, we investigated ACE2 protein abundance in patients either requiring mechanical ventilation or spontaneously breathing. ACE2 distribution and expression were determined in archival lung samples by immunohistochemistry (IHC). Tissues were selected from the specimen inventory at a large teaching hospital collected between 2010–2020. Twelve samples were chosen from patients receiving mechanical ventilation for acute hypoxic respiratory failure (AHRF). Twenty samples were selected from patients not requiring ventilation. We compared samples across age, ranging from 40–83 years old in the ventilated cohort and 14–80 years old in the non-ventilated cohort. Within the alveolated parenchyma, ACE2 expression is predominantly observed in type II pneumocytes (or alveolar type II / AT2 cells) and alveolar macrophages. All 12 samples from our ventilated cohort showed histologic features of diffuse alveolar damage including reactive, proliferating AT2 cells. In these cases, ACE2 was strongly upregulated with age when normalized to lung area (p = 0.004) or cellularity (p = 0.003), associated with prominent expression in AT2 cells. In non-ventilated individuals, AT2 cell reactive changes were not observed and ACE2 expression did not change with age when normalized to lung area (p = 0.231) or cellularity (p = 0.349). In summary, ACE2 expression increases with age in the setting of alveolar damage observed in patients on mechanical ventilation, providing a potential mechanism for higher Covid-19 mortality in the elderly. |
format | Online Article Text |
id | pubmed-7886150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-78861502021-02-23 Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation Baker, Steven Andrew Kwok, Shirley Berry, Gerald J. Montine, Thomas J. PLoS One Research Article Mortality due to Covid-19 is highly associated with advanced age, owing in large part to severe lower respiratory tract infection. SARS-CoV-2 utilizes the host ACE2 receptor for infection. Whether ACE2 abundance in the lung contributes to age-associated vulnerability is currently unknown. We set out to characterize the RNA and protein expression profiles of ACE2 in aging human lung in the context of phenotypic parameters likely to affect lung physiology. Examining publicly available RNA sequencing data, we discovered that mechanical ventilation is a critical variable affecting lung ACE2 levels. Therefore, we investigated ACE2 protein abundance in patients either requiring mechanical ventilation or spontaneously breathing. ACE2 distribution and expression were determined in archival lung samples by immunohistochemistry (IHC). Tissues were selected from the specimen inventory at a large teaching hospital collected between 2010–2020. Twelve samples were chosen from patients receiving mechanical ventilation for acute hypoxic respiratory failure (AHRF). Twenty samples were selected from patients not requiring ventilation. We compared samples across age, ranging from 40–83 years old in the ventilated cohort and 14–80 years old in the non-ventilated cohort. Within the alveolated parenchyma, ACE2 expression is predominantly observed in type II pneumocytes (or alveolar type II / AT2 cells) and alveolar macrophages. All 12 samples from our ventilated cohort showed histologic features of diffuse alveolar damage including reactive, proliferating AT2 cells. In these cases, ACE2 was strongly upregulated with age when normalized to lung area (p = 0.004) or cellularity (p = 0.003), associated with prominent expression in AT2 cells. In non-ventilated individuals, AT2 cell reactive changes were not observed and ACE2 expression did not change with age when normalized to lung area (p = 0.231) or cellularity (p = 0.349). In summary, ACE2 expression increases with age in the setting of alveolar damage observed in patients on mechanical ventilation, providing a potential mechanism for higher Covid-19 mortality in the elderly. Public Library of Science 2021-02-16 /pmc/articles/PMC7886150/ /pubmed/33592054 http://dx.doi.org/10.1371/journal.pone.0247060 Text en © 2021 Baker et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Baker, Steven Andrew Kwok, Shirley Berry, Gerald J. Montine, Thomas J. Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation |
title | Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation |
title_full | Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation |
title_fullStr | Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation |
title_full_unstemmed | Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation |
title_short | Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation |
title_sort | angiotensin-converting enzyme 2 (ace2) expression increases with age in patients requiring mechanical ventilation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886150/ https://www.ncbi.nlm.nih.gov/pubmed/33592054 http://dx.doi.org/10.1371/journal.pone.0247060 |
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